{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/118209","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/37164731","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=397418","label":"url"}],"paper_title":{"en":"Effects of EOS789, a novel pan-phosphate transporter inhibitor, on phosphate metabolism : Comparison with a conventional phosphate binder","ja":"Effects of EOS789, a novel pan-phosphate transporter inhibitor, on phosphate metabolism : Comparison with a conventional phosphate binder"},"authors":{"en":[{"name":"Tanifuji Kazuya"},{"name":"Shiozaki Yuji"},{"name":"Koike Megumi"},{"name":"Uga Minori"},{"name":"Miura Mizuki"},{"name":"Higashi Ayami"},{"name":"Shimohata Takaaki"},{"name":"Takahashi Akira"},{"name":"Hayashi Hisayoshi"},{"name":"Ishizuka Noriko"},{"name":"Ichida Yasuhiro"},{"name":"Ohtomo Shuichi"},{"name":"Horiba Naoshi"},{"name":"Miyamoto Ken-ichi"},{"name":"Segawa Hiroko"}],"ja":[{"name":"谷藤 和也"},{"name":"塩﨑 雄治"},{"name":"小池 萌"},{"name":"宇賀 穂"},{"name":"三浦 美月"},{"name":"東 彩生"},{"name":"下畑 隆明"},{"name":"髙橋 章"},{"name":"Hayashi Hisayoshi"},{"name":"Ishizuka Noriko"},{"name":"Ichida Yasuhiro"},{"name":"Ohtomo Shuichi"},{"name":"Horiba Naoshi"},{"name":"宮本 賢一"},{"name":"瀬川 博子"}]},"description":{"en":"Inorganic phosphate (Pi) binders are the only pharmacologic treatment approved for hyperphosphatemia. However, Pi binders induce the expression of intestinal Pi transporters and have limited effects on the inhibition of Pi transport. EOS789, a novel pan-Pi transporter inhibitor, reportedly has potent efficacy in treating hyperphosphatemia. We investigated the properties of EOS789 with comparison to a conventional Pi binder. Protein and mRNA expression levels of Pi transporters were measured in intestinal and kidney tissues from male Wistar rats fed diets supplemented with EOS789 or lanthanum carbonate (LC). 32Pi permeability was measured in intestinal tissues from normal rats using a chamber. Increased protein levels of NaPi-2b, an intestinal Pi transporter, and luminal Pi removal were observed in rats treated with LC but not in rats treated with EOS789. EOS789 but not LC suppressed intestinal protein levels of the Pi transporter Pit-1 and sodium/hydrogen exchanger isoform 3. 32Pi flux experiments using small intestine tissues from rats demonstrated that EOS789 may affect transcellular Pi transport in addition to paracellular Pi transport. EOS789 has differing regulatory effects on Pi metabolism compared to LC. The properties of EOS789 may compensate for the limitations of LC therapy. The combined or selective use of EOS789 and conventional Pi binders may allow tighter control of hyperphosphatemia. J. Med. Invest. 70 : 260-270, February, 2023.","ja":"Inorganic phosphate (Pi) binders are the only pharmacologic treatment approved for hyperphosphatemia. However, Pi binders induce the expression of intestinal Pi transporters and have limited effects on the inhibition of Pi transport. EOS789, a novel pan-Pi transporter inhibitor, reportedly has potent efficacy in treating hyperphosphatemia. We investigated the properties of EOS789 with comparison to a conventional Pi binder. Protein and mRNA expression levels of Pi transporters were measured in intestinal and kidney tissues from male Wistar rats fed diets supplemented with EOS789 or lanthanum carbonate (LC). 32Pi permeability was measured in intestinal tissues from normal rats using a chamber. Increased protein levels of NaPi-2b, an intestinal Pi transporter, and luminal Pi removal were observed in rats treated with LC but not in rats treated with EOS789. EOS789 but not LC suppressed intestinal protein levels of the Pi transporter Pit-1 and sodium/hydrogen exchanger isoform 3. 32Pi flux experiments using small intestine tissues from rats demonstrated that EOS789 may affect transcellular Pi transport in addition to paracellular Pi transport. EOS789 has differing regulatory effects on Pi metabolism compared to LC. The properties of EOS789 may compensate for the limitations of LC therapy. The combined or selective use of EOS789 and conventional Pi binders may allow tighter control of hyperphosphatemia. J. Med. Invest. 70 : 260-270, February, 2023."},"publication_date":"2023","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.70","number":"No.1,2","starting_page":"260","ending_page":"270","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.70.260"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/35428804","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=387857","label":"url"}],"paper_title":{"en":"Tmem174, a regulator of phosphate transporter prevents hyperphosphatemia.","ja":"Tmem174, a regulator of phosphate transporter prevents hyperphosphatemia."},"authors":{"en":[{"name":"Sasaki Sumire"},{"name":"Shiozaki Yuji"},{"name":"Hanazaki Ai"},{"name":"Koike Megumi"},{"name":"Tanifuji Kazuya"},{"name":"Uga Minori"},{"name":"Kawahara Kota"},{"name":"Kaneko Ichiro"},{"name":"Kawamoto Yasuharu"},{"name":"Wiriyasermkul Pattama"},{"name":"Hasegawa Tomoka"},{"name":"Amizuka Norio"},{"name":"Miyamoto Ken-ichi"},{"name":"Nagamori Shushi"},{"name":"Kanai Yoshikatsu"},{"name":"Segawa Hiroko"}],"ja":[{"name":"佐々木 すみれ"},{"name":"塩﨑 雄治"},{"name":"花崎 愛"},{"name":"小池 萌"},{"name":"谷藤 和也"},{"name":"宇賀 穂"},{"name":"Kawahara Kota"},{"name":"金子 一郎"},{"name":"Kawamoto Yasuharu"},{"name":"Wiriyasermkul Pattama"},{"name":"Hasegawa Tomoka"},{"name":"Amizuka Norio"},{"name":"宮本 賢一"},{"name":"Nagamori Shushi"},{"name":"Kanai Yoshikatsu"},{"name":"瀬川 博子"}]},"description":{"en":"Renal type II sodium-dependent inorganic phosphate (Pi) transporters NaPi2a and NaPi2c cooperate with other organs to strictly regulate the plasma Pi concentration. A high Pi load induces expression and secretion of the phosphaturic hormones parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) that enhance urinary Pi excretion and prevent the onset of hyperphosphatemia. How FGF23 secretion from bone is increased by a high Pi load and the setpoint of the plasma Pi concentration, however, are unclear. Here, we investigated the role of Transmembrane protein 174 (Tmem174) and observed evidence for gene co-expression networks in NaPi2a and NaPi2c function. Tmem174 is localized in the renal proximal tubules and interacts with NaPi2a, but not NaPi2c. In Tmem174-knockout (KO) mice, the serum FGF23 concentration was markedly increased but increased Pi excretion and hypophosphatemia were not observed. In addition, Tmem174-KO mice exhibit reduced NaPi2a responsiveness to FGF23 and PTH administration. Furthermore, a dietary Pi load causes marked hyperphosphatemia and abnormal NaPi2a regulation in Tmem174-KO mice. Thus, Tmem174 is thought to be associated with FGF23 induction in bones and the regulation of NaPi2a to prevent an increase in the plasma Pi concentration due to a high Pi load and kidney injury.","ja":"Renal type II sodium-dependent inorganic phosphate (Pi) transporters NaPi2a and NaPi2c cooperate with other organs to strictly regulate the plasma Pi concentration. A high Pi load induces expression and secretion of the phosphaturic hormones parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) that enhance urinary Pi excretion and prevent the onset of hyperphosphatemia. How FGF23 secretion from bone is increased by a high Pi load and the setpoint of the plasma Pi concentration, however, are unclear. Here, we investigated the role of Transmembrane protein 174 (Tmem174) and observed evidence for gene co-expression networks in NaPi2a and NaPi2c function. Tmem174 is localized in the renal proximal tubules and interacts with NaPi2a, but not NaPi2c. In Tmem174-knockout (KO) mice, the serum FGF23 concentration was markedly increased but increased Pi excretion and hypophosphatemia were not observed. In addition, Tmem174-KO mice exhibit reduced NaPi2a responsiveness to FGF23 and PTH administration. Furthermore, a dietary Pi load causes marked hyperphosphatemia and abnormal NaPi2a regulation in Tmem174-KO mice. Thus, Tmem174 is thought to be associated with FGF23 induction in bones and the regulation of NaPi2a to prevent an increase in the plasma Pi concentration due to a high Pi load and kidney injury."},"publication_date":"2022-04-15","publication_name":{"en":"Scientific Reports","ja":"Scientific Reports"},"volume":"Vol.12","number":"No.1","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1038/s41598-022-10409-3"],"issn":["2045-2322"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/117148","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/36244766","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-85139886601&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=387841","label":"url"}],"paper_title":{"en":"Dietary polyphosphate has a greater effect on renal damage and FGF23 secretion than dietary monophosphate","ja":"Dietary polyphosphate has a greater effect on renal damage and FGF23 secretion than dietary monophosphate"},"authors":{"en":[{"name":"Sasaki Sumire"},{"name":"Koike Megumi"},{"name":"Tanifuji Kazuya"},{"name":"Uga Minori"},{"name":"Kawahara Kota"},{"name":"Komiya Aoi"},{"name":"Miura Mizuki"},{"name":"Harada Yamato"},{"name":"Hamaguchi Yuki"},{"name":"Sasaki Shohei"},{"name":"Shiozaki Yuji"},{"name":"Kaneko Ichiro"},{"name":"Miyamoto Ken-ichi"},{"name":"Segawa Hiroko"}],"ja":[{"name":"佐々木 すみれ"},{"name":"小池 萌"},{"name":"谷藤 和也"},{"name":"宇賀 穂"},{"name":"川原 滉太"},{"name":"小宮 蒼"},{"name":"三浦 美月"},{"name":"原田 和"},{"name":"濵口 ゆき"},{"name":"佐々木 祥平"},{"name":"塩﨑 雄治"},{"name":"金子 一郎"},{"name":"宮本 賢一"},{"name":"瀬川 博子"}]},"description":{"en":"Phosphate (Pi)-containing food additives are used in several forms. Polyphosphate (PPi) salt has more harmful effects than monophosphate (MPi) salt on bone physiology and renal function. This study aimed to analyze the levels of parathyroid hormone PTH and fibroblast growth factor 23 (FGF23) and the expression of renal / intestinal Pi transport-related molecules in mice fed with an MPi or PPi diet. There were no significant differences in plasma Pi concentration and fecal Pi excretion levels between mice fed with the high-MPi and PPi diet. However, more severe tubular dilatation, interstitial fibrosis, and calcification were observed in the kidneys of mice fed with the high PPi diet versus the MPi diet. Furthermore, there was a significant increase in serum FGF23 levels and a decrease in renal phosphate transporter protein expression in mice fed with the PPi diet versus the MPi diet. Furthermore, the high MPi diet was associated with significantly suppressed expression and activity of intestinal alkaline phosphatase protein. In summary, PPi has a more severe effect on renal damage than MPi, as well as induces more FGF23 secretion. Excess FGF23 may be more involved in inflammation, fibrosis, and calcification in the kidney. J. Med. Invest. 69 : 173-179, August, 2022.","ja":"Phosphate (Pi)-containing food additives are used in several forms. Polyphosphate (PPi) salt has more harmful effects than monophosphate (MPi) salt on bone physiology and renal function. This study aimed to analyze the levels of parathyroid hormone PTH and fibroblast growth factor 23 (FGF23) and the expression of renal / intestinal Pi transport-related molecules in mice fed with an MPi or PPi diet. There were no significant differences in plasma Pi concentration and fecal Pi excretion levels between mice fed with the high-MPi and PPi diet. However, more severe tubular dilatation, interstitial fibrosis, and calcification were observed in the kidneys of mice fed with the high PPi diet versus the MPi diet. Furthermore, there was a significant increase in serum FGF23 levels and a decrease in renal phosphate transporter protein expression in mice fed with the PPi diet versus the MPi diet. Furthermore, the high MPi diet was associated with significantly suppressed expression and activity of intestinal alkaline phosphatase protein. In summary, PPi has a more severe effect on renal damage than MPi, as well as induces more FGF23 secretion. Excess FGF23 may be more involved in inflammation, fibrosis, and calcification in the kidney. J. Med. Invest. 69 : 173-179, August, 2022."},"publication_date":"2022","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.69","number":"No.3","starting_page":"173","ending_page":"179","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.69.173"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30895530","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=355024","label":"url"}],"paper_title":{"en":"Role of the putative PKC phosphorylation sites of the type IIc sodium-dependent phosphate transporter in parathyroid hormone regulation.","ja":"Role of the putative PKC phosphorylation sites of the type IIc sodium-dependent phosphate transporter in parathyroid hormone regulation."},"authors":{"en":[{"name":"Fujii Toru"},{"name":"Segawa Hiroko"},{"name":"Hanazaki Ai"},{"name":"Nishiguchi Shiori"},{"name":"Minoshima Sakura"},{"name":"Ohi Akiko"},{"name":"Tominaga Rieko"},{"name":"Sasaki Sumire"},{"name":"Tanifuji Kazuya"},{"name":"Koike Megumi"},{"name":"Arima Yuki"},{"name":"Shiozaki Yuji"},{"name":"Kaneko Ichiro"},{"name":"Ito Mikiko"},{"name":"Tatsumi Sawako"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Fujii Toru"},{"name":"瀬川 博子"},{"name":"Hanazaki Ai"},{"name":"Nishiguchi Shiori"},{"name":"Minoshima Sakura"},{"name":"Ohi Akiko"},{"name":"Tominaga Rieko"},{"name":"Sasaki Sumire"},{"name":"Tanifuji Kazuya"},{"name":"Koike Megumi"},{"name":"Arima Yuki"},{"name":"Shiozaki Yuji"},{"name":"金子 一郎"},{"name":"Ito Mikiko"},{"name":"Tatsumi Sawako"},{"name":"宮本 賢一"}]},"publication_date":"2019-03-21","publication_name":{"en":"Clinical and Experimental Nephrology","ja":"Clinical and Experimental Nephrology"},"volume":"Vol.23","number":"No.7","starting_page":"898","ending_page":"907","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s10157-019-01725-6"],"issn":["1437-7799"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30523405","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=355023","label":"url"}],"paper_title":{"en":"Systemic network for dietary inorganic phosphate adaptation among three organs.","ja":"Systemic network for dietary inorganic phosphate adaptation among three organs."},"authors":{"en":[{"name":"Ikuta Kayo"},{"name":"Segawa Hiroko"},{"name":"Hanazaki Ai"},{"name":"Fujii Toru"},{"name":"Kaneko Ichiro"},{"name":"Shiozaki Yuji"},{"name":"Tatsumi Sawako"},{"name":"Ishikawa Yasuko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Ikuta Kayo"},{"name":"瀬川 博子"},{"name":"Hanazaki Ai"},{"name":"Fujii Toru"},{"name":"金子 一郎"},{"name":"Shiozaki Yuji"},{"name":"Tatsumi Sawako"},{"name":"Ishikawa Yasuko"},{"name":"宮本 賢一"}]},"publication_date":"2018-12-06","publication_name":{"en":"Pflügers Archiv : European Journal of Physiology","ja":"Pflügers Archiv : European Journal of Physiology"},"volume":"Vol.471","number":"No.1","starting_page":"123","ending_page":"136","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00424-018-2242-9"],"issn":["1432-2013"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/113363","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30317447","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=355022","label":"url"}],"paper_title":{"en":"Analysis of opossum kidney NaPi-IIc sodium-dependent phosphate transporter to understand Pi handling in human kidney.","ja":"Analysis of opossum kidney NaPi-IIc sodium-dependent phosphate transporter to understand Pi handling in human kidney."},"authors":{"en":[{"name":"Fujii Toru"},{"name":"Shiozaki Yuji"},{"name":"Segawa Hiroko"},{"name":"Nishiguchi Shiori"},{"name":"Hanazaki Ai"},{"name":"Noguchi Miwa"},{"name":"Kirino Ruri"},{"name":"Sasaki Sumire"},{"name":"Tanifuji Kazuya"},{"name":"Koike Megumi"},{"name":"Yokoyama Mizuki"},{"name":"Arima Yuki"},{"name":"Kaneko Ichiro"},{"name":"Tatsumi Sawako"},{"name":"Ito Mikiko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Fujii Toru"},{"name":"Shiozaki Yuji"},{"name":"瀬川 博子"},{"name":"Nishiguchi Shiori"},{"name":"Hanazaki Ai"},{"name":"Noguchi Miwa"},{"name":"Kirino Ruri"},{"name":"Sasaki Sumire"},{"name":"Tanifuji Kazuya"},{"name":"Koike Megumi"},{"name":"Yokoyama Mizuki"},{"name":"Arima Yuki"},{"name":"金子 一郎"},{"name":"Tatsumi Sawako"},{"name":"Ito Mikiko"},{"name":"宮本 賢一"}]},"publication_date":"2018-10-13","publication_name":{"en":"Clinical and Experimental Nephrology","ja":"Clinical and Experimental Nephrology"},"volume":"Vol.23","number":"No.3","starting_page":"313","ending_page":"324","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s10157-018-1653-4"],"issn":["1437-7799"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/112882","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/30212831","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=355018","label":"url"}],"paper_title":{"en":"A Role of Intestinal Alkaline Phosphatase 3 (Akp3) in Inorganic Phosphate Homeostasis.","ja":"A Role of Intestinal Alkaline Phosphatase 3 (Akp3) in Inorganic Phosphate Homeostasis."},"authors":{"en":[{"name":"Sasaki Shohei"},{"name":"Segawa Hiroko"},{"name":"Hanazaki Ai"},{"name":"Kirino Ruri"},{"name":"Fujii Toru"},{"name":"Ikuta Kayo"},{"name":"Noguchi Miwa"},{"name":"Sasaki Sumire"},{"name":"Koike Megumi"},{"name":"Tanifuji Kazuya"},{"name":"Shiozaki Yuji"},{"name":"Kaneko Ichiro"},{"name":"Tatsumi Sawako"},{"name":"Shimohata Takaaki"},{"name":"Kawai Yoshichika"},{"name":"Narisawa Sonoko"},{"name":"Millán José Luis"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Sasaki Shohei"},{"name":"瀬川 博子"},{"name":"Hanazaki Ai"},{"name":"Kirino Ruri"},{"name":"Fujii Toru"},{"name":"Ikuta Kayo"},{"name":"Noguchi Miwa"},{"name":"Sasaki Sumire"},{"name":"Koike Megumi"},{"name":"Tanifuji Kazuya"},{"name":"Shiozaki Yuji"},{"name":"金子 一郎"},{"name":"Tatsumi Sawako"},{"name":"下畑 隆明"},{"name":"Kawai Yoshichika"},{"name":"Narisawa Sonoko"},{"name":"Millán José Luis"},{"name":"宮本 賢一"}]},"publication_date":"2018-09-13","publication_name":{"en":"Kidney & Blood Pressure Research","ja":"Kidney & Blood Pressure Research"},"volume":"Vol.43","number":"No.5","starting_page":"1409","ending_page":"1424","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1159/000493379"],"issn":["1423-0143"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29878089","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=343891","label":"url"}],"paper_title":{"en":"Eldecalcitol Causes FGF23 Resistance for Pi Reabsorption and Improves Rachitic Bone Phenotypes in the Male Hyp Mouse.","ja":"Eldecalcitol Causes FGF23 Resistance for Pi Reabsorption and Improves Rachitic Bone Phenotypes in the Male Hyp Mouse."},"authors":{"en":[{"name":"Kaneko Ichiro"},{"name":"Segawa Hiroko"},{"name":"Kayo Ikuta"},{"name":"Ai Hanazaki"},{"name":"Toru Fujii"},{"name":"Tatsumi Sawako"},{"name":"Shinsuke Kido"},{"name":"Tomoka Hasegawa"},{"name":"Norio Amizuka"},{"name":"Hitoshi Saito"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"金子 一郎"},{"name":"瀬川 博子"},{"name":"Kayo Ikuta"},{"name":"Ai Hanazaki"},{"name":"Toru Fujii"},{"name":"辰巳 佐和子"},{"name":"Shinsuke Kido"},{"name":"Tomoka Hasegawa"},{"name":"Norio Amizuka"},{"name":"Hitoshi Saito"},{"name":"宮本 賢一"}]},"description":{"en":"X-linked hypophosphatemia (XLH), the most common form of inheritable rickets, is caused by inactivation of phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and leads to fibroblast growth factor (FGF) 23-dependent renal inorganic phosphate (Pi) wasting. In the present study, we investigated whether maintaining Pi homeostasis with a potent vitamin D3 analog, eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxypropyloxy) vitamin D3; ED71], could improve hypophosphatemic rickets in a murine model of XLH, the Hyp mouse. Vehicle, ED71, or 1,25-dihydroxyvitamin D was subcutaneously injected five times weekly in wild-type (WT) and Hyp mice for 4 weeks, from 4 to 8 weeks of age. Injection of ED71 into WT mice suppressed the synthesis of renal 1,25-dihydroxyvitamin D and promoted phosphaturic activity. In contrast, administration of ED71 to Hyp mice completely restored renal Pi transport and NaPi-2a protein levels, although the plasma-intact FGF23 levels were further increased. In addition, ED71 markedly increased the levels of the scaffold proteins, renal sodium-hydrogen exchanger regulatory factor 1, and ezrin in the Hyp mouse kidney. Treatment with ED71 increased the body weight and improved hypophosphatemia, the bone volume/total volume, bone mineral content, and growth plate structure in Hyp mice. Thus, ED71 causes FGF23 resistance for phosphate reabsorption and improves rachitic bone phenotypes in Hyp mice. In conclusion, ED71 has opposite effects on phosphate homeostasis in WT and Hyp mice. Analysis of Hyp mice treated with ED71 could result in an additional model for elucidating PHEX abnormalities.","ja":"X-linked hypophosphatemia (XLH), the most common form of inheritable rickets, is caused by inactivation of phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and leads to fibroblast growth factor (FGF) 23-dependent renal inorganic phosphate (Pi) wasting. In the present study, we investigated whether maintaining Pi homeostasis with a potent vitamin D3 analog, eldecalcitol [1α,25-dihydroxy-2β-(3-hydroxypropyloxy) vitamin D3; ED71], could improve hypophosphatemic rickets in a murine model of XLH, the Hyp mouse. Vehicle, ED71, or 1,25-dihydroxyvitamin D was subcutaneously injected five times weekly in wild-type (WT) and Hyp mice for 4 weeks, from 4 to 8 weeks of age. Injection of ED71 into WT mice suppressed the synthesis of renal 1,25-dihydroxyvitamin D and promoted phosphaturic activity. In contrast, administration of ED71 to Hyp mice completely restored renal Pi transport and NaPi-2a protein levels, although the plasma-intact FGF23 levels were further increased. In addition, ED71 markedly increased the levels of the scaffold proteins, renal sodium-hydrogen exchanger regulatory factor 1, and ezrin in the Hyp mouse kidney. Treatment with ED71 increased the body weight and improved hypophosphatemia, the bone volume/total volume, bone mineral content, and growth plate structure in Hyp mice. Thus, ED71 causes FGF23 resistance for phosphate reabsorption and improves rachitic bone phenotypes in Hyp mice. In conclusion, ED71 has opposite effects on phosphate homeostasis in WT and Hyp mice. Analysis of Hyp mice treated with ED71 could result in an additional model for elucidating PHEX abnormalities."},"publication_date":"2018-07-01","publication_name":{"en":"Endocrinology","ja":"Endocrinology"},"volume":"Vol.159","number":"No.7","starting_page":"2741","ending_page":"2758","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1210/en.2018-00109"],"issn":["1945-7170"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111600","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29398136","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=342186","label":"url"}],"paper_title":{"en":"The sodium phosphate cotransporter family and nicotinamide phosphoribosyltransferase contribute to the daily oscillation of plasma inorganic phosphate concentration.","ja":"The sodium phosphate cotransporter family and nicotinamide phosphoribosyltransferase contribute to the daily oscillation of plasma inorganic phosphate concentration."},"authors":{"en":[{"name":"Miyagawa Atsumi"},{"name":"Tatsumi Sawako"},{"name":"Takahama Wako"},{"name":"Fujii Osamu"},{"name":"Nagamoto Kenta"},{"name":"Kinoshita Emi"},{"name":"Nomura Kengo"},{"name":"Ikuta Kayo"},{"name":"Fujii Toru"},{"name":"Hanazaki Ai"},{"name":"Kaneko Ichiro"},{"name":"Segawa Hiroko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Miyagawa Atsumi"},{"name":"辰巳 佐和子"},{"name":"Takahama Wako"},{"name":"Fujii Osamu"},{"name":"Nagamoto Kenta"},{"name":"Kinoshita Emi"},{"name":"Nomura Kengo"},{"name":"Ikuta Kayo"},{"name":"Fujii Toru"},{"name":"Hanazaki Ai"},{"name":"金子 一郎"},{"name":"瀬川 博子"},{"name":"宮本 賢一"}]},"description":{"en":"mice, NAD levels were significantly reduced in the liver, kidney, and intestine, and the daily oscillation (active and rest phases) of the plasma phosphate concentration was attenuated. Thus, the Nampt/NAD","ja":"system for Npt2 regulation and cellular shifts to tissues such as the liver play an important role in generating daily oscillation of plasma inorganic phosphate levels."},"publication_date":"2018-02-15","publication_name":{"en":"Kidney International","ja":"Kidney International"},"volume":"Vol.93","number":"No.5","starting_page":"1073","ending_page":"1085","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.kint.2017.11.022"],"issn":["1523-1755"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/112958","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29312149","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=342187","label":"url"}],"paper_title":{"en":"Effect of Osteocyte-Ablation on Inorganic Phosphate Metabolism: Analysis of Bone-Kidney-Gut Axis.","ja":"Effect of Osteocyte-Ablation on Inorganic Phosphate Metabolism: Analysis of Bone-Kidney-Gut Axis."},"authors":{"en":[{"name":"Fujii Osamu"},{"name":"Tatsumi Sawako"},{"name":"Ogata Mao"},{"name":"Arakaki Tomohiro"},{"name":"Sakaguchi Haruna"},{"name":"Nomura Kengo"},{"name":"Miyagawa Atsumi"},{"name":"Ikuta Kayo"},{"name":"Hanazaki Ai"},{"name":"Kaneko Ichiro"},{"name":"Segawa Hiroko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Fujii Osamu"},{"name":"辰巳 佐和子"},{"name":"Ogata Mao"},{"name":"Arakaki Tomohiro"},{"name":"Sakaguchi Haruna"},{"name":"Nomura Kengo"},{"name":"Miyagawa Atsumi"},{"name":"Ikuta Kayo"},{"name":"Hanazaki Ai"},{"name":"金子 一郎"},{"name":"瀬川 博子"},{"name":"宮本 賢一"}]},"description":{"en":"In response to kidney damage, osteocytes increase the production of several hormones critically involved in mineral metabolism. Recent studies suggest that osteocyte function is altered very early in the course of chronic kidney disease. In the present study, to clarify the role of osteocytes and the canalicular network in mineral homeostasis, we performed four experiments. In Experiment 1, we investigated renal and intestinal Pi handling in osteocyte-less (OCL) model mice [transgenic mice with the dentin matrix protein-1 promoter-driven diphtheria toxin (DT)-receptor that were injected with DT]. In Experiment 2, we administered granulocyte colony-stimulating factor to mice to disrupt the osteocyte canalicular network. In Experiment 3, we investigated the role of osteocytes in dietary Pi signaling. In Experiment 4, we analyzed gene expression level fluctuations in the intestine and liver by comparing mice fed a high Pi diet and OCL mice. Together, the findings of these experiments indicate that osteocyte ablation caused rapid renal Pi excretion (","ja":"< 0.01), thus suggesting that increased intestinal Pi absorption stimulates renal Pi excretion in OCL mice. In addition, the ablation of osteocytes and feeding of a high Pi diet affected FGF15/bile acid metabolism and controlled Npt2b expression. In conclusion, OCL mice exhibited increased renal Pi excretion due to enhanced intestinal Pi absorption. We discuss the role of FGF23-Klotho on renal and intestinal Pi metabolism in OCL mice."},"publication_date":"2017-12-21","publication_name":{"en":"Frontiers in Endocrinology","ja":"Frontiers in Endocrinology"},"volume":"Vol.8","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3389/fendo.2017.00359"],"issn":["1664-2392"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111601","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/29128884","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=342185","label":"url"}],"paper_title":{"en":"Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling.","ja":"Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling."},"authors":{"en":[{"name":"Ikuta Kayo"},{"name":"Segawa Hiroko"},{"name":"Sasaki Shohei"},{"name":"Hanazaki Ai"},{"name":"Fujii Toru"},{"name":"Kushi Aoi"},{"name":"Kawabata Yuka"},{"name":"Kirino Ruri"},{"name":"Sasaki Sumire"},{"name":"Noguchi Miwa"},{"name":"Kaneko Ichiro"},{"name":"Tatsumi Sawako"},{"name":"Ueda Otoya"},{"name":"Wada Naoko"},{"name":"Tateishi Hiromi"},{"name":"Kakefuda Mami"},{"name":"Kawase Yosuke"},{"name":"Ohtomo Shuichi"},{"name":"Ichida Yasuhiro"},{"name":"Maeda Akira"},{"name":"Jishage Kou-Ichi"},{"name":"Horiba Naoshi"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"生田 かよ"},{"name":"瀬川 博子"},{"name":"佐々木 祥平"},{"name":"花崎 愛"},{"name":"Fujii Toru"},{"name":"串 葵"},{"name":"川端 優佳"},{"name":"桐野 留里"},{"name":"佐々木 すみれ"},{"name":"野口 実和"},{"name":"金子 一郎"},{"name":"辰巳 佐和子"},{"name":"Ueda Otoya"},{"name":"Wada Naoko"},{"name":"Tateishi Hiromi"},{"name":"Kakefuda Mami"},{"name":"Kawase Yosuke"},{"name":"Ohtomo Shuichi"},{"name":"Ichida Yasuhiro"},{"name":"前田 彰"},{"name":"Jishage Kou-Ichi"},{"name":"Horiba Naoshi"},{"name":"宮本 賢一"}]},"description":{"en":"These findings indicate that abnormal Pi metabolism may also be involved in tight junction molecules such as Cldns that are affected by Npt2b deficiency.","ja":"-dependent Pi transport in brush-border membrane vesicle uptake levels was significantly decreased in the distal intestine of Npt2b CKO mice compared with control mice, plasma Pi and fecal Pi excretion levels were not significantly different. Data obtained using the intestinal loop technique showed that Pi uptake in Npt2b CKO mice was not affected at a Pi concentration of 4 mM, which is considered the typical luminal Pi concentration after meals in mice. Claudin, which may be involved in paracellular pathways, as well as claudin-2, 12, and 15 protein levels were significantly decreased in the Npt2b CKO mice. Thus, Npt2b deficiency did not affect Pi absorption within the range of Pi concentrations that normally occurs after meals."},"publication_date":"2017-11-11","publication_name":{"en":"Clinical and Experimental Nephrology","ja":"Clinical and Experimental Nephrology"},"volume":"Vol.22","number":"No.3","starting_page":"517","ending_page":"528","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s10157-017-1497-3"],"issn":["1437-7799"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26296817","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=333718","label":"url"}],"paper_title":{"en":"Regulation of renal phosphate handling: inter-organ communication in health and disease.","ja":"Regulation of renal phosphate handling: inter-organ communication in health and disease."},"authors":{"en":[{"name":"Tatsumi Sawako"},{"name":"Miyagawa A"},{"name":"Kaneko Ichiro"},{"name":"Shiozaki Y"},{"name":"Segawa Hiroko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"辰巳 佐和子"},{"name":"Miyagawa A"},{"name":"金子 一郎"},{"name":"Shiozaki Y"},{"name":"瀬川 博子"},{"name":"宮本 賢一"}]},"description":{"en":"In this review, we focus on the interconnection of inorganic phosphate (Pi) homeostasis in the network of the bone-kidney, parathyroid-kidney, intestine-kidney, and liver-kidney axes. Such a network of organ communication is important for body Pi homeostasis. Normalization of serum Pi levels is a clinical target in patients with chronic kidney disease (CKD). Particularly, disorders of the fibroblast growth factor 23/klotho system are observed in early CKD. Identification of phosphaturic factors from the intestine and liver may enhance our understanding of body Pi homeostasis and Pi metabolism disturbances in CKD patients.","ja":"In this review, we focus on the interconnection of inorganic phosphate (Pi) homeostasis in the network of the bone-kidney, parathyroid-kidney, intestine-kidney, and liver-kidney axes. Such a network of organ communication is important for body Pi homeostasis. Normalization of serum Pi levels is a clinical target in patients with chronic kidney disease (CKD). Particularly, disorders of the fibroblast growth factor 23/klotho system are observed in early CKD. Identification of phosphaturic factors from the intestine and liver may enhance our understanding of body Pi homeostasis and Pi metabolism disturbances in CKD patients."},"publication_date":"2016-01","publication_name":{"en":"Journal of Bone and Mineral Metabolism","ja":"Journal of Bone and Mineral Metabolism"},"volume":"Vol.34","number":"No.1","starting_page":"1","ending_page":"10","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00774-015-0705-z"],"issn":["1435-5604"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=296570","label":"url"}],"paper_title":{"en":"Clinical Nutrition education in Japanese dietitians","ja":"Clinical Nutrition education in Japanese dietitians"},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"Tatsumi Sawako"},{"name":"Hamada Yasuhiro"}],"ja":[{"name":"宮本 賢一"},{"name":"辰巳 佐和子"},{"name":"濵田 康弘"}]},"publication_date":"2015-06-26","publication_name":{"en":"第60回日本透析医学会","ja":"第60回日本透析医学会"},"languages":["eng"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111281","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26399350","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84942042069&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=316929","label":"url"}],"paper_title":{"en":"Relationship between sodium-dependent phosphate transporter (NaPi-IIc) function and cellular vacuole formation in opossum kidney cells.","ja":"Relationship between sodium-dependent phosphate transporter (NaPi-IIc) function and cellular vacuole formation in opossum kidney cells."},"authors":{"en":[{"name":"Shiozaki Yuji"},{"name":"Segawa Hiroko"},{"name":"Ohnishi Saori"},{"name":"Ohi Akiko"},{"name":"Ito Mikiko"},{"name":"Kaneko Ichiro"},{"name":"Kido Shinsuke"},{"name":"Tatsumi Sawako"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Shiozaki Yuji"},{"name":"瀬川 博子"},{"name":"Ohnishi Saori"},{"name":"Ohi Akiko"},{"name":"Ito Mikiko"},{"name":"金子 一郎"},{"name":"Kido Shinsuke"},{"name":"辰巳 佐和子"},{"name":"宮本 賢一"}]},"description":{"en":"NaPi-IIc/SLC34A3 is a sodium-dependent inorganic phosphate (Pi) transporter in the renal proximal tubules and its mutations cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). In the present study, we created a specific antibody for opossum SLC34A3, NaPi-IIc (oNaPi-IIc), and analyzed its localization and regulation in opossum kidney cells (a tissue culture model of proximal tubular cells). Immunoreactive oNaPi-IIc protein levels increased during the proliferative phase and decreased during differentiation. Moreover, stimulating cell growth upregulated oNaPi-IIc protein levels, whereas suppressing cell proliferation downregulated oNaPi-IIc protein levels. Immunocytochemistry revealed that endogenous and exogenous oNaPi-IIc proteins localized at the protrusion of the plasma membrane, which is a phosphatidylinositol 4,5-bisphosphate (PIP2) rich-membrane, and at the intracellular vacuolar membrane. Exogenous NaPi-IIc also induced cellular vacuoles and localized in the plasma membrane. The ability to form vacuoles is specific to electroneutral NaPi-IIc, and not electrogenic NaPi-IIa or NaPi-IIb. In addition, mutations of NaPi-IIc (S138F and R468W) in HHRH did not cause cellular PIP2-rich vacuoles. In conclusion, our data anticipate that NaPi-IIc may regulate PIP2 production at the plasma membrane and cellular vesicle formation.","ja":"NaPi-IIc/SLC34A3 is a sodium-dependent inorganic phosphate (Pi) transporter in the renal proximal tubules and its mutations cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). In the present study, we created a specific antibody for opossum SLC34A3, NaPi-IIc (oNaPi-IIc), and analyzed its localization and regulation in opossum kidney cells (a tissue culture model of proximal tubular cells). Immunoreactive oNaPi-IIc protein levels increased during the proliferative phase and decreased during differentiation. Moreover, stimulating cell growth upregulated oNaPi-IIc protein levels, whereas suppressing cell proliferation downregulated oNaPi-IIc protein levels. Immunocytochemistry revealed that endogenous and exogenous oNaPi-IIc proteins localized at the protrusion of the plasma membrane, which is a phosphatidylinositol 4,5-bisphosphate (PIP2) rich-membrane, and at the intracellular vacuolar membrane. Exogenous NaPi-IIc also induced cellular vacuoles and localized in the plasma membrane. The ability to form vacuoles is specific to electroneutral NaPi-IIc, and not electrogenic NaPi-IIa or NaPi-IIb. In addition, mutations of NaPi-IIc (S138F and R468W) in HHRH did not cause cellular PIP2-rich vacuoles. In conclusion, our data anticipate that NaPi-IIc may regulate PIP2 production at the plasma membrane and cellular vesicle formation."},"publication_date":"2015-06-01","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.62","number":"No.3-4","starting_page":"209","ending_page":"218","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.62.209"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/26598845","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84950314636&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=306624","label":"url"}],"paper_title":{"en":"Niacin and Chronic Kidney Disease.","ja":"Niacin and Chronic Kidney Disease."},"authors":{"en":[{"name":"Taketani Yutaka"},{"name":"Masuda Masashi"},{"name":"Okumura Hisami"},{"name":"Tatsumi Sawako"},{"name":"Segawa Hiroko"},{"name":"Miyamoto Ken-ichi"},{"name":"Takeda Eiji"},{"name":"Yamamoto Hironori"}],"ja":[{"name":"竹谷 豊"},{"name":"増田 真志"},{"name":"奥村 仙示"},{"name":"辰巳 佐和子"},{"name":"瀬川 博子"},{"name":"宮本 賢一"},{"name":"武田 英二"},{"name":"山本 浩範"}]},"description":{"en":"Chronic kidney disease (CKD) is an increasing problem worldwide. The number of end-stage renal disease patients requiring treatment by dialysis is estimated to be increasing by 10,000 patients per year in Japan. Furthermore, an estimated 13 million people are living with CKD in Japan. Various complications are associated with CKD, including cardiovascular disease (CVD). More than one-third of CKD patients die from CVD. Thus, prevention of CVD is a primary concern for the treatment of CKD patients. CKD-mineral and bone disorder (CKD-MBD) is a serious complication that typically leads to CVD. Hyperphosphatemia is thought to be a central-risk factor for CKD-MBD. Therefore, managing hyperphosphatemia is crucial to prevent CKD-MBD and CVD. It is difficult to achieve the target serum phosphate level through dietary modifications alone in patients with hyperphosphatemia, because most foods contain phosphate. Thus, phosphate binders such as calcium carbonate are commonly prescribed to CKD patients with hyperphosphatemia, but these have undesirable side effects. Inhibition of intestinal phosphate transport activity has also been investigated as an alternative approach for controlling serum phosphate levels in CKD patients. Nicotinamide, which is the amide of niacin, can inhibit intestinal phosphate transport. Niacin and related compounds have also been developed as drugs for hyperlipidemia conditions, especially hypertriglyceridemia with low high-density lipoprotein. This type of dyslipidemia is frequently observed in CKD patients and is a modifiable risk factor for CVD. Thus, niacin and related compounds may have utility for the treatment of both hyperphosphatemia and dyslipidemia in CKD patients to prevent CVD.","ja":"Chronic kidney disease (CKD) is an increasing problem worldwide. The number of end-stage renal disease patients requiring treatment by dialysis is estimated to be increasing by 10,000 patients per year in Japan. Furthermore, an estimated 13 million people are living with CKD in Japan. Various complications are associated with CKD, including cardiovascular disease (CVD). More than one-third of CKD patients die from CVD. Thus, prevention of CVD is a primary concern for the treatment of CKD patients. CKD-mineral and bone disorder (CKD-MBD) is a serious complication that typically leads to CVD. Hyperphosphatemia is thought to be a central-risk factor for CKD-MBD. Therefore, managing hyperphosphatemia is crucial to prevent CKD-MBD and CVD. It is difficult to achieve the target serum phosphate level through dietary modifications alone in patients with hyperphosphatemia, because most foods contain phosphate. Thus, phosphate binders such as calcium carbonate are commonly prescribed to CKD patients with hyperphosphatemia, but these have undesirable side effects. Inhibition of intestinal phosphate transport activity has also been investigated as an alternative approach for controlling serum phosphate levels in CKD patients. Nicotinamide, which is the amide of niacin, can inhibit intestinal phosphate transport. Niacin and related compounds have also been developed as drugs for hyperlipidemia conditions, especially hypertriglyceridemia with low high-density lipoprotein. This type of dyslipidemia is frequently observed in CKD patients and is a modifiable risk factor for CVD. Thus, niacin and related compounds may have utility for the treatment of both hyperphosphatemia and dyslipidemia in CKD patients to prevent CVD."},"publication_date":"2015","publication_name":{"en":"Journal of Nutritional Science and Vitaminology","ja":"Journal of Nutritional Science and Vitaminology"},"volume":"Vol.61 Suppl","starting_page":"S173","ending_page":"5","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3177/jnsv.61.S173"],"issn":["1881-7742"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/106156","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24262791","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=283008","label":"url"}],"paper_title":{"en":"Hepatectomy-related hypophosphatemia: a novel phosphaturic factor in the liver-kidney axis.","ja":"Hepatectomy-related hypophosphatemia: a novel phosphaturic factor in the liver-kidney axis."},"authors":{"en":[{"name":"Nomura Kengo"},{"name":"Tatsumi Sawako"},{"name":"Miyagawa Atsumi"},{"name":"Shiozaki Yuji"},{"name":"Sasaki Shohei"},{"name":"Kaneko Ichiro"},{"name":"Ito Mikiko"},{"name":"Kido Shinsuke"},{"name":"Segawa Hiroko"},{"name":"Sano Mitsue"},{"name":"Fukuwatari Tsutomu"},{"name":"Shibata Katsumi"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Nomura Kengo"},{"name":"辰巳 佐和子"},{"name":"Miyagawa Atsumi"},{"name":"Shiozaki Yuji"},{"name":"Sasaki Shohei"},{"name":"金子 一郎"},{"name":"伊藤 美紀子"},{"name":"木戸 慎介"},{"name":"瀬川 博子"},{"name":"Sano Mitsue"},{"name":"Fukuwatari Tsutomu"},{"name":"Shibata Katsumi"},{"name":"宮本 賢一"}]},"description":{"en":"Marked hypophosphatemia is common after major hepatic resection, but the pathophysiologic mechanism remains unknown. We used a partial hepatectomy (PH) rat model to investigate the molecular basis of hypophosphatemia. PH rats exhibited hypophosphatemia and hyperphosphaturia. In renal and intestinal brush-border membrane vesicles isolated from PH rats, Na(+)-dependent phosphate (Pi) uptake decreased by 50%-60%. PH rats also exhibited significantly decreased levels of renal and intestinal Na(+)-dependent Pi transporter proteins (NaPi-IIa [NaPi-4], NaPi-IIb, and NaPi-IIc). Parathyroid hormone was elevated at 6 hours after PH. Hyperphosphaturia persisted, however, even after thyroparathyroidectomy in PH rats. Moreover, DNA microarray data revealed elevated levels of nicotinamide phosphoribosyltransferase (Nampt) mRNA in the kidney after PH, and Nampt protein levels and total NAD concentration increased significantly in the proximal tubules. PH rats also exhibited markedly increased levels of the Nampt substrate, urinary nicotinamide (NAM), and NAM catabolites. In vitro analyses using opossum kidney cells revealed that NAM alone did not affect endogenous NaPi-4 levels. However, in cells overexpressing Nampt, the addition of NAM led to a marked decrease in cell surface expression of NaPi-4 that was blocked by treatment with FK866, a specific Nampt inhibitor. Furthermore, FK866-treated mice showed elevated renal Pi reabsorption and hypophosphaturia. These findings indicate that hepatectomy-induced hypophosphatemia is due to abnormal NAM metabolism, including Nampt activation in renal proximal tubular cells.","ja":"Marked hypophosphatemia is common after major hepatic resection, but the pathophysiologic mechanism remains unknown. We used a partial hepatectomy (PH) rat model to investigate the molecular basis of hypophosphatemia. PH rats exhibited hypophosphatemia and hyperphosphaturia. In renal and intestinal brush-border membrane vesicles isolated from PH rats, Na(+)-dependent phosphate (Pi) uptake decreased by 50%-60%. PH rats also exhibited significantly decreased levels of renal and intestinal Na(+)-dependent Pi transporter proteins (NaPi-IIa [NaPi-4], NaPi-IIb, and NaPi-IIc). Parathyroid hormone was elevated at 6 hours after PH. Hyperphosphaturia persisted, however, even after thyroparathyroidectomy in PH rats. Moreover, DNA microarray data revealed elevated levels of nicotinamide phosphoribosyltransferase (Nampt) mRNA in the kidney after PH, and Nampt protein levels and total NAD concentration increased significantly in the proximal tubules. PH rats also exhibited markedly increased levels of the Nampt substrate, urinary nicotinamide (NAM), and NAM catabolites. In vitro analyses using opossum kidney cells revealed that NAM alone did not affect endogenous NaPi-4 levels. However, in cells overexpressing Nampt, the addition of NAM led to a marked decrease in cell surface expression of NaPi-4 that was blocked by treatment with FK866, a specific Nampt inhibitor. Furthermore, FK866-treated mice showed elevated renal Pi reabsorption and hypophosphaturia. These findings indicate that hepatectomy-induced hypophosphatemia is due to abnormal NAM metabolism, including Nampt activation in renal proximal tubular cells."},"publication_date":"2014-04","publication_name":{"en":"Journal of the American Society of Nephrology","ja":"Journal of the American Society of Nephrology"},"volume":"Vol.25","number":"No.4","starting_page":"761","ending_page":"772","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1681/ASN.2013060569"],"issn":["1533-3450"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24614234","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84899983795&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=279475","label":"url"}],"paper_title":{"en":"Molecular mechanisms of cadmium-induced fibroblast growth factor 23 upregulation in osteoblast-like cells.","ja":"Molecular mechanisms of cadmium-induced fibroblast growth factor 23 upregulation in osteoblast-like cells."},"authors":{"en":[{"name":"Kido Shinsuke"},{"name":"Fujihara Marina"},{"name":"Nomura Kengo"},{"name":"Sasaki Shohei"},{"name":"Mukai Rie"},{"name":"Ohnishi Ritsuko"},{"name":"Kaneko Ichiro"},{"name":"Segawa Hiroko"},{"name":"Tatsumi Sawako"},{"name":"Izumi Hiroto"},{"name":"Kohno Kimitoshi"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"木戸 慎介"},{"name":"Fujihara Marina"},{"name":"Nomura Kengo"},{"name":"Sasaki Shohei"},{"name":"向井 理恵"},{"name":"Ohnishi Ritsuko"},{"name":"金子 一郎"},{"name":"瀬川 博子"},{"name":"辰巳 佐和子"},{"name":"Izumi Hiroto"},{"name":"Kohno Kimitoshi"},{"name":"宮本 賢一"}]},"description":{"en":"Itai-itai disease is thought to be the result of chronic cadmium (Cd) intoxication. Renal proximal tubules are a major target of Cd toxicity. The whole mechanism of the adverse effects of Cd remains unresolved, especially how renal damage is related to the development of bone lesions. Fibroblast growth factor 23 (FGF23) is a bone-derived phosphaturic factor that regulates vitamin D and inorganic phosphate metabolism in the kidney. To clarify the role of FGF23 on Cd toxicity, we investigated the mechanisms of Cd-induced FGF23 production in the bone. Cd injection into mice significantly increased plasma FGF23 concentrations, but did not change FGF23 mRNA expression in bone. GalNAc-T3 is involved in secreting intact FGF23. To determine potential roles of GalNAc-T3 in Cd-induced FGF23 production, we examined the effect of Cd on GalNAc-T3 mRNA expression in vivo and in vitro. GalNAc-T3 gene expression was significantly increased in the bones of Cd-injected mice. Cd also enhanced the expression of GalNAc-T3 in cultured osteosarcoma UMR106 cells and primary osteocytes. Cd activated aryl hydrocarbon receptors (AhR) and AhR were required for GalNAc-T3 gene expression induced by Cd. In addition, Cd-dependent FGF23 production was completely inhibited by an AhR antagonist. AhR siRNA markedly suppressed the stimulation of transcriptional activity by Cd. Furthermore, Cd induced AhR activation via phosphorylation of Ser-68 by p38 kinase in the nuclear export signal of AhR. Thus, Cd stimulated GalNAc-T3 gene transcription via enhanced AhR binding to the GalNAc-T3 promoter. These findings suggest that the Cd-induced increase in GalNAc-T3 suppresses proteolytic processing of FGF23 and increases serum FGF23 concentrations.","ja":"Itai-itai disease is thought to be the result of chronic cadmium (Cd) intoxication. Renal proximal tubules are a major target of Cd toxicity. The whole mechanism of the adverse effects of Cd remains unresolved, especially how renal damage is related to the development of bone lesions. Fibroblast growth factor 23 (FGF23) is a bone-derived phosphaturic factor that regulates vitamin D and inorganic phosphate metabolism in the kidney. To clarify the role of FGF23 on Cd toxicity, we investigated the mechanisms of Cd-induced FGF23 production in the bone. Cd injection into mice significantly increased plasma FGF23 concentrations, but did not change FGF23 mRNA expression in bone. GalNAc-T3 is involved in secreting intact FGF23. To determine potential roles of GalNAc-T3 in Cd-induced FGF23 production, we examined the effect of Cd on GalNAc-T3 mRNA expression in vivo and in vitro. GalNAc-T3 gene expression was significantly increased in the bones of Cd-injected mice. Cd also enhanced the expression of GalNAc-T3 in cultured osteosarcoma UMR106 cells and primary osteocytes. Cd activated aryl hydrocarbon receptors (AhR) and AhR were required for GalNAc-T3 gene expression induced by Cd. In addition, Cd-dependent FGF23 production was completely inhibited by an AhR antagonist. AhR siRNA markedly suppressed the stimulation of transcriptional activity by Cd. Furthermore, Cd induced AhR activation via phosphorylation of Ser-68 by p38 kinase in the nuclear export signal of AhR. Thus, Cd stimulated GalNAc-T3 gene transcription via enhanced AhR binding to the GalNAc-T3 promoter. These findings suggest that the Cd-induced increase in GalNAc-T3 suppresses proteolytic processing of FGF23 and increases serum FGF23 concentrations."},"publication_date":"2014-03-10","publication_name":{"en":"Toxicological Sciences","ja":"Toxicological Sciences"},"volume":"Vol.139","number":"No.2","starting_page":"301","ending_page":"316","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1093/toxsci/kfu043"],"issn":["1096-0929"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/106159","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24688219","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=298337","label":"url"}],"paper_title":{"en":"Short-term dietary phosphate restriction up-regulates ileal fibroblast growth factor 15 gene expression in mice.","ja":"Short-term dietary phosphate restriction up-regulates ileal fibroblast growth factor 15 gene expression in mice."},"authors":{"en":[{"name":"Nakahashi Otoki"},{"name":"Yamamoto Hironori"},{"name":"Tanaka Sarasa"},{"name":"Kozai Mina"},{"name":"Takei Yuichiro"},{"name":"Masuda Masashi"},{"name":"Kaneko Ichiro"},{"name":"Taketani Yutaka"},{"name":"Iwano Masayuki"},{"name":"Miyamoto Ken-ichi"},{"name":"Takeda Eiji"}],"ja":[{"name":"Nakahashi Otoki"},{"name":"山本 浩範"},{"name":"Tanaka Sarasa"},{"name":"Kozai Mina"},{"name":"Takei Yuichiro"},{"name":"増田 真志"},{"name":"金子 一郎"},{"name":"竹谷 豊"},{"name":"Iwano Masayuki"},{"name":"宮本 賢一"},{"name":"武田 英二"}]},"description":{"en":"Members of the fibroblast growth factor (FGF) 19 subfamily, including FGF23, FGF15/19, and FGF21, have a role as endocrine factors which influence the metabolism of inorganic phosphate (Pi) and vitamin D, bile acid, and energy. It has been reported that dietary Pi regulates circulating FGF23. In this study, the short-term effects of dietary Pi restriction on the expression of FGF19 subfamily members in mice were analyzed. An initial analysis confirmed plasma FGF23 levels positively correlated with the amount of dietary Pi. On the other hand, ileal Fgf15 gene expression, but not hepatic Fgf21 gene expression, was up-regulated by dietary Pi restriction. In addition, we observed the increase of plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] levels by dietary Pi restriction, and the up-regulation of ileal Fgf15 mRNA expression by 1,25(OH)2D3 and vitamin D receptor (VDR). Importantly, dietary Pi restriction-induced Fgf15 gene expression was prevented in VDR-knockout mice. Furthermore, diurnal variations of plasma triglyceride concentrations and hepatic mRNA expression of the bile acid synthesis enzyme Cyp7a1 as one of Fgf15 negative target genes was influenced by dietary Pi restriction. These results suggest that dietary Pi restriction up-regulates ileal Fgf15 gene expression through 1,25(OH)2D3 and VDR, and may affect hepatic bile acid homeostasis.","ja":"Members of the fibroblast growth factor (FGF) 19 subfamily, including FGF23, FGF15/19, and FGF21, have a role as endocrine factors which influence the metabolism of inorganic phosphate (Pi) and vitamin D, bile acid, and energy. It has been reported that dietary Pi regulates circulating FGF23. In this study, the short-term effects of dietary Pi restriction on the expression of FGF19 subfamily members in mice were analyzed. An initial analysis confirmed plasma FGF23 levels positively correlated with the amount of dietary Pi. On the other hand, ileal Fgf15 gene expression, but not hepatic Fgf21 gene expression, was up-regulated by dietary Pi restriction. In addition, we observed the increase of plasma 1,25-dihydroxyvitamin D [1,25(OH)2D] levels by dietary Pi restriction, and the up-regulation of ileal Fgf15 mRNA expression by 1,25(OH)2D3 and vitamin D receptor (VDR). Importantly, dietary Pi restriction-induced Fgf15 gene expression was prevented in VDR-knockout mice. Furthermore, diurnal variations of plasma triglyceride concentrations and hepatic mRNA expression of the bile acid synthesis enzyme Cyp7a1 as one of Fgf15 negative target genes was influenced by dietary Pi restriction. These results suggest that dietary Pi restriction up-regulates ileal Fgf15 gene expression through 1,25(OH)2D3 and VDR, and may affect hepatic bile acid homeostasis."},"publication_date":"2014-03-01","publication_name":{"en":"Journal of Clinical Biochemistry and Nutrition","ja":"Journal of Clinical Biochemistry and Nutrition"},"volume":"Vol.54","number":"No.2","starting_page":"102","ending_page":"108","languages":["eng"],"referee":true,"identifiers":{"doi":["10.3164/jcbn.13-109"],"issn":["0912-0009"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/106168","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24500689","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=283001","label":"url"}],"paper_title":{"en":"Downregulation of renal type IIa sodium-dependent phosphate cotransporter during lipopolysaccharide-induced acute inflammation.","ja":"Downregulation of renal type IIa sodium-dependent phosphate cotransporter during lipopolysaccharide-induced acute inflammation."},"authors":{"en":[{"name":"Ikeda Shoko"},{"name":"Yamamoto Hironori"},{"name":"Masuda Masashi"},{"name":"Takei Yuichiro"},{"name":"Nakahashi Otoki"},{"name":"Kozai Mina"},{"name":"Tanaka Sarasa"},{"name":"Nakao Mari"},{"name":"Taketani Yutaka"},{"name":"Segawa Hiroko"},{"name":"Iwano Masayuki"},{"name":"Miyamoto Ken-ichi"},{"name":"Takeda Eiji"}],"ja":[{"name":"Ikeda Shoko"},{"name":"Yamamoto Hironori"},{"name":"増田 真志"},{"name":"Takei Yuichiro"},{"name":"Nakahashi Otoki"},{"name":"Kozai Mina"},{"name":"Tanaka Sarasa"},{"name":"Nakao Mari"},{"name":"竹谷 豊"},{"name":"瀬川 博子"},{"name":"Iwano Masayuki"},{"name":"宮本 賢一"},{"name":"武田 英二"}]},"description":{"en":"The type IIa sodium-dependent phosphate cotransporter (Npt2a) plays a critical role in reabsorption of inorganic phosphate (Pi) by renal proximal tubular cells. Pi abnormalities during early stages of sepsis have been reported, but the mechanisms regulating Pi homeostasis during acute inflammation are poorly understood. We examined the regulation of Pi metabolism and renal Npt2a expression during lipopolysaccharide (LPS)-induced inflammation in mice. Dose-response and time-course studies with LPS showed significant increases of plasma Pi and intact parathyroid hormone (iPTH) levels and renal Pi excretion, while renal calcium excretion was significantly decreased. There was no difference in plasma 1,25-dihydroxyvitamin D levels, but the induction of plasma intact fibroblast growth factor 23 levels peaked 3 h after LPS treatment. Western blotting, immunostaining, and quantitative real-time PCR showed that LPS administration significantly decreased Npt2a protein expression in the brush border membrane (BBM) 3 h after injection, but there was no change in renal Npt2a mRNA levels. Moreover, tumor necrosis factor- injection also increased plasma iPTH and decreased renal BBM Npt2a expression. Importantly, we revealed that parathyroidectomized rats had impaired renal Pi excretion and BBM Npt2a expression in response to LPS. These results suggest that the downregulation of Npt2a expression in renal BBM through induction of plasma iPTH levels alter Pi homeostasis during LPS-induced acute inflammation.","ja":"The type IIa sodium-dependent phosphate cotransporter (Npt2a) plays a critical role in reabsorption of inorganic phosphate (Pi) by renal proximal tubular cells. Pi abnormalities during early stages of sepsis have been reported, but the mechanisms regulating Pi homeostasis during acute inflammation are poorly understood. We examined the regulation of Pi metabolism and renal Npt2a expression during lipopolysaccharide (LPS)-induced inflammation in mice. Dose-response and time-course studies with LPS showed significant increases of plasma Pi and intact parathyroid hormone (iPTH) levels and renal Pi excretion, while renal calcium excretion was significantly decreased. There was no difference in plasma 1,25-dihydroxyvitamin D levels, but the induction of plasma intact fibroblast growth factor 23 levels peaked 3 h after LPS treatment. Western blotting, immunostaining, and quantitative real-time PCR showed that LPS administration significantly decreased Npt2a protein expression in the brush border membrane (BBM) 3 h after injection, but there was no change in renal Npt2a mRNA levels. Moreover, tumor necrosis factor- injection also increased plasma iPTH and decreased renal BBM Npt2a expression. Importantly, we revealed that parathyroidectomized rats had impaired renal Pi excretion and BBM Npt2a expression in response to LPS. These results suggest that the downregulation of Npt2a expression in renal BBM through induction of plasma iPTH levels alter Pi homeostasis during LPS-induced acute inflammation."},"publication_date":"2014-02-05","publication_name":{"en":"American Journal of Physiology, Renal Physiology","ja":"American Journal of Physiology, Renal Physiology"},"volume":"Vol.306","number":"No.7","starting_page":"F744","ending_page":"50","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajprenal.00474.2013"],"issn":["1522-1466"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/130004822704/","label":"url"},{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/109545","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24705762","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390001204244658176/","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84897932982&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=282998","label":"url"}],"paper_title":{"en":"Effect of dietary components on renal inorganic phosphate (Pi) excretion induced by a Pi-depleted diet.","ja":"Effect of dietary components on renal inorganic phosphate (Pi) excretion induced by a Pi-depleted diet."},"authors":{"en":[{"name":"Ohnishi Ritsuko"},{"name":"Segawa Hiroko"},{"name":"Ohmoto Tomoyo"},{"name":"Sasaki Shohei"},{"name":"Hanazaki Ai"},{"name":"Mori Ayaka"},{"name":"Ikuta Kayo"},{"name":"Furutani Junya"},{"name":"Kawakami Eri"},{"name":"Tatsumi Sawako"},{"name":"Hamada Yasuhiro"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Ohnishi Ritsuko"},{"name":"瀬川 博子"},{"name":"Ohmoto Tomoyo"},{"name":"Sasaki Shohei"},{"name":"Hanazaki Ai"},{"name":"Mori Ayaka"},{"name":"Ikuta Kayo"},{"name":"Furutani Junya"},{"name":"Kawakami Eri"},{"name":"辰巳 佐和子"},{"name":"濵田 康弘"},{"name":"宮本 賢一"}]},"description":{"en":"Dietary inorganic phosphate (Pi) is the most important factor in the regulation of renal Pi excretion. Recent studies suggest the presence of an enteric-renal signaling axis for dietary Pi as well as the existence of a mechanism by which the intestine detects changes in luminal Pi concentrations. The mechanisms of intestinal Pi sensing, however, are unknown. In the present study, we focused on Pi depletion signals and investigated the effects of dietary components on intestinal Pi sensing. After feeding rats experimental diets for 3 days, we investigated urinary Pi excretion and plasma biochemical parameters. Renal Pi excretion was suppressed in rats fed a low-Pi diet (0.02% Pi). Elimination of dietary calcium (Ca) completely blocked the suppression of Pi excretion, suggesting that the presence of Ca is essential for the Pi depletion signal. Furthermore, a minimum Ca content of more than 0.02% was necessary for the Pi depletion signal. Magnesium, lanthanum, and strontium, which are agonists of calcium sensing receptor, instead of Ca, reduced Pi excretion. Therefore, dietary Ca appears to be important for the Pi depletion-sensing mechanism in the gastrointestinal tract. In addition, the calcium sensing receptor may be involved in the Pi depletion signal.","ja":"Dietary inorganic phosphate (Pi) is the most important factor in the regulation of renal Pi excretion. Recent studies suggest the presence of an enteric-renal signaling axis for dietary Pi as well as the existence of a mechanism by which the intestine detects changes in luminal Pi concentrations. The mechanisms of intestinal Pi sensing, however, are unknown. In the present study, we focused on Pi depletion signals and investigated the effects of dietary components on intestinal Pi sensing. After feeding rats experimental diets for 3 days, we investigated urinary Pi excretion and plasma biochemical parameters. Renal Pi excretion was suppressed in rats fed a low-Pi diet (0.02% Pi). Elimination of dietary calcium (Ca) completely blocked the suppression of Pi excretion, suggesting that the presence of Ca is essential for the Pi depletion signal. Furthermore, a minimum Ca content of more than 0.02% was necessary for the Pi depletion signal. Magnesium, lanthanum, and strontium, which are agonists of calcium sensing receptor, instead of Ca, reduced Pi excretion. Therefore, dietary Ca appears to be important for the Pi depletion-sensing mechanism in the gastrointestinal tract. In addition, the calcium sensing receptor may be involved in the Pi depletion signal."},"publication_date":"2014","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.61","number":"No.1-2","starting_page":"162","ending_page":"170","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.61.162"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/23397032","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=268578","label":"url"}],"paper_title":{"en":"Parathyroid hormone (1-34) counteracts the suppression of interleukin-11 expression by glucocorticoid in murine osteoblasts: a possible mechanism for stimulating osteoblast differentiation against glucocorticoid excess.","ja":"Parathyroid hormone (1-34) counteracts the suppression of interleukin-11 expression by glucocorticoid in murine osteoblasts: a possible mechanism for stimulating osteoblast differentiation against glucocorticoid excess."},"authors":{"en":[{"name":"Kuriwaka-Kido Rika"},{"name":"Kido Shinsuke"},{"name":"Miyatani Yuka"},{"name":"Ito Yuji"},{"name":"Kondo Takeshi"},{"name":"Omatsu Takashi"},{"name":"Dong Bingzi"},{"name":"Endo Itsuro"},{"name":"Miyamoto Ken-ichi"},{"name":"Matsumoto Toshio"}],"ja":[{"name":"Kuriwaka-Kido Rika"},{"name":"Kido Shinsuke"},{"name":"Miyatani Yuka"},{"name":"Ito Yuji"},{"name":"近藤 剛史"},{"name":"Omatsu Takashi"},{"name":"Dong Bingzi"},{"name":"遠藤 逸朗"},{"name":"宮本 賢一"},{"name":"松本 俊夫"}]},"description":{"en":"Glucocorticoid (GC) excess causes a rapid loss of bone with a reduction in bone formation. Intermittent PTH (1-34) administration stimulates bone formation and counteracts the inhibition of bone formation by GC excess. We have previously demonstrated that mechanical strain enhances interleukin (IL)-11 gene transcription by a rapid induction of FosB expression and protein kinase C (PKC)--mediated phosphorylation of phosphorylated mothers against decapentaplegic (Smad)-1. Because IL-11 suppresses the expression of dickkopf-1 and -2 and stimulates Wnt signaling, IL-11 appears to mediate at least a part of the effect of mechanical strain on osteoblast differentiation and bone formation. The present study was undertaken to examine the effect of PTH(1-34) and GCs on IL-11 expression in murine primary osteoblasts (mPOBs). PTH(1-34) treatment of mPOBs enhanced IL-11 expression in a time- and dose-dependent manner. PTH(1-34) also stimulated FosB expression and Smad1 phosphorylation, which cooperatively stimulated IL-11 gene transcription. PTH(1-34)-induced Smad1 phosphorylation was mediated via PKC and was abrogated in mPOBs from PKC knockout mice. Dexamethasone suppressed IL-11 gene transcription enhanced by PTH(1-34) without affecting FosB expression or Smad1 phosphorylation, and dexamethasone-GC receptor complex was bound to JunD, which forms heterodimers with FosB. High doses of PTH(1-34) counteracted the effect of dexamethasone on apoptosis of mPOBs, which was blunted by neutralizing anti-IL-11 antibody or IL-11 small interfering RNA. These results demonstrate that PTH(1-34) and GCs interact to regulate IL-11 expression in parallel with osteoblast differentiation and apoptosis and suggest that PTH(1-34) and dexamethasone may regulate osteoblast differentiation and apoptosis via their effect on IL-11 expression.","ja":"Glucocorticoid (GC) excess causes a rapid loss of bone with a reduction in bone formation. Intermittent PTH (1-34) administration stimulates bone formation and counteracts the inhibition of bone formation by GC excess. We have previously demonstrated that mechanical strain enhances interleukin (IL)-11 gene transcription by a rapid induction of FosB expression and protein kinase C (PKC)--mediated phosphorylation of phosphorylated mothers against decapentaplegic (Smad)-1. Because IL-11 suppresses the expression of dickkopf-1 and -2 and stimulates Wnt signaling, IL-11 appears to mediate at least a part of the effect of mechanical strain on osteoblast differentiation and bone formation. The present study was undertaken to examine the effect of PTH(1-34) and GCs on IL-11 expression in murine primary osteoblasts (mPOBs). PTH(1-34) treatment of mPOBs enhanced IL-11 expression in a time- and dose-dependent manner. PTH(1-34) also stimulated FosB expression and Smad1 phosphorylation, which cooperatively stimulated IL-11 gene transcription. PTH(1-34)-induced Smad1 phosphorylation was mediated via PKC and was abrogated in mPOBs from PKC knockout mice. Dexamethasone suppressed IL-11 gene transcription enhanced by PTH(1-34) without affecting FosB expression or Smad1 phosphorylation, and dexamethasone-GC receptor complex was bound to JunD, which forms heterodimers with FosB. High doses of PTH(1-34) counteracted the effect of dexamethasone on apoptosis of mPOBs, which was blunted by neutralizing anti-IL-11 antibody or IL-11 small interfering RNA. These results demonstrate that PTH(1-34) and GCs interact to regulate IL-11 expression in parallel with osteoblast differentiation and apoptosis and suggest that PTH(1-34) and dexamethasone may regulate osteoblast differentiation and apoptosis via their effect on IL-11 expression."},"publication_date":"2013-02-08","publication_name":{"en":"Endocrinology","ja":"Endocrinology"},"volume":"Vol.154","number":"No.3","starting_page":"1156","ending_page":"1167","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1210/en.2013-1915"],"issn":["1945-7170"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/106356","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/24190035","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84887001043&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=284880","label":"url"}],"paper_title":{"en":"Hypercholesterolemia and effects of high cholesterol diet in type IIa sodium-dependent phosphate co-transporter (Npt2a) deficient mice.","ja":"Hypercholesterolemia and effects of high cholesterol diet in type IIa sodium-dependent phosphate co-transporter (Npt2a) deficient mice."},"authors":{"en":[{"name":"Tanaka Sarasa"},{"name":"Yamamoto Hironori"},{"name":"Nakahashi Otoki"},{"name":"Ishiguro Mariko"},{"name":"Takei Yuichiro"},{"name":"Masuda Masashi"},{"name":"Kozai Mina"},{"name":"Ikeda Shoko"},{"name":"Taketani Yutaka"},{"name":"Miyamoto Ken-ichi"},{"name":"Takeda Eiji"}],"ja":[{"name":"Tanaka Sarasa"},{"name":"山本 浩範"},{"name":"Nakahashi Otoki"},{"name":"Ishiguro Mariko"},{"name":"Takei Yuichiro"},{"name":"増田 真志"},{"name":"Kozai Mina"},{"name":"Ikeda Shoko"},{"name":"竹谷 豊"},{"name":"宮本 賢一"},{"name":"武田 英二"}]},"description":{"en":"The type IIa sodium-dependent phosphate co-transporter (Npt2a) is important to maintain renal inorganic phosphate (Pi) homeostasis and the plasma Pi levels. It has reported that disorder of Pi metabolism in kidney can be risk factors for cardiovascular disease as well as hypercholesterolemia. However, the relationship between Pi and cholesterol metabolism has not been clarified. The current study investigated the effects of Npt2a gene ablation that is known as hypophosphatemia model on cholesterol metabolism in mice. Npt2a deficient (Npt2a(-/-)) mice and wild type mice were fed diets with or without 2% cholesterol for 12 days. Plasma lipid and lipoprotein profile analysis revealed that plasma lipid levels (total, LDL and HDL cholesterol) were significantly higher in Npt2a(-/-) mice than wild type (WT) mice. Interestingly, high cholesterol diet markedly increased plasma levels of total, LDL and HDL cholesterol in WT mice, but not Npt2a(-/-) mice. On the other hand, there were no differences in body and liver weight, intake and hepatic lipid accumulation between WT and Npt2a(-/-) mice. These results suggest that ablation of Npt2a gene induces hypercholesterolemia and affects the ability to respond normally to dietary cholesterol.","ja":"The type IIa sodium-dependent phosphate co-transporter (Npt2a) is important to maintain renal inorganic phosphate (Pi) homeostasis and the plasma Pi levels. It has reported that disorder of Pi metabolism in kidney can be risk factors for cardiovascular disease as well as hypercholesterolemia. However, the relationship between Pi and cholesterol metabolism has not been clarified. The current study investigated the effects of Npt2a gene ablation that is known as hypophosphatemia model on cholesterol metabolism in mice. Npt2a deficient (Npt2a(-/-)) mice and wild type mice were fed diets with or without 2% cholesterol for 12 days. Plasma lipid and lipoprotein profile analysis revealed that plasma lipid levels (total, LDL and HDL cholesterol) were significantly higher in Npt2a(-/-) mice than wild type (WT) mice. Interestingly, high cholesterol diet markedly increased plasma levels of total, LDL and HDL cholesterol in WT mice, but not Npt2a(-/-) mice. On the other hand, there were no differences in body and liver weight, intake and hepatic lipid accumulation between WT and Npt2a(-/-) mice. These results suggest that ablation of Npt2a gene induces hypercholesterolemia and affects the ability to respond normally to dietary cholesterol."},"publication_date":"2013","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.60","number":"No.3-4","starting_page":"191","ending_page":"196","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.60.191"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=271074","label":"url"}],"paper_title":{"en":"FGF23の作用と作用機序.","ja":"FGF23の作用と作用機序."},"authors":{"en":[{"name":"Kido Shinsuke"},{"name":"Kuwahara Shoji"},{"name":"Nomura Kengo"},{"name":"Ohi Akiko"},{"name":"Tatsumi Sawako"},{"name":"Segawa Hiroko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"木戸 慎介"},{"name":"桑原 頌治"},{"name":"野村 憲吾"},{"name":"大井 彰子"},{"name":"辰巳 佐和子"},{"name":"瀬川 博子"},{"name":"宮本 賢一"}]},"publication_date":"2012-01-01","starting_page":"25","ending_page":"31","languages":["jpn"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/106008","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22450000","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=291140","label":"url"}],"paper_title":{"en":"Identification and functional analysis of a splice variant of mouse sodium-dependent phosphate transporter Npt2c.","ja":"Identification and functional analysis of a splice variant of mouse sodium-dependent phosphate transporter Npt2c."},"authors":{"en":[{"name":"Kuwahara Shoji"},{"name":"Aranami Fumito"},{"name":"Segawa Hiroko"},{"name":"Onitsuka Akemi"},{"name":"Honda Naoko"},{"name":"Tominaga Rieko"},{"name":"Hanabusa Etsuyo"},{"name":"Kaneko Ichiro"},{"name":"Yamanaka Setsuko"},{"name":"Sasaki Shohei"},{"name":"Ohi Akiko"},{"name":"Nomura Kengo"},{"name":"Tatsumi Sawako"},{"name":"Kido Shinsuke"},{"name":"Ito Mikiko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Kuwahara Shoji"},{"name":"Aranami Fumito"},{"name":"瀬川 博子"},{"name":"Onitsuka Akemi"},{"name":"Honda Naoko"},{"name":"Tominaga Rieko"},{"name":"Hanabusa Etsuyo"},{"name":"金子 一郎"},{"name":"Yamanaka Setsuko"},{"name":"Sasaki Shohei"},{"name":"Ohi Akiko"},{"name":"Nomura Kengo"},{"name":"辰巳 佐和子"},{"name":"木戸 慎介"},{"name":"伊藤 美紀子"},{"name":"宮本 賢一"}]},"description":{"en":"Mutations in the SLC34A3 gene, a sodium-dependent inorganic phosphate (Pi) cotransporter, also referred to as NaPi IIc, causes hereditary hypophosphatemic rickets with hypercalciuria (HHRH), an autosomal recessive disorder. In human and rodent, NaPi IIc is mainly localized in the apical membrane of renal proximal tubular cells. In this study, we identified mouse NaPi IIc variant (Npt2c-v1) that lacks the part of the exon 3 sequence that includes the assumed translation initiation site of Npt2c. Microinjection of mouse Npt2c-v1 cRNA into Xenopus oocytes demonstrated that Npt2c-v1 showed sodium-dependent Pi cotransport activity. The characterization of pH dependency showed activation at extracellular alkaline-pH. Furthermore, Npt2c-v1 mediated Pi transport activity was significantly higher at any pH value than those of Npt2c. In an in vitro study, the localization of the Npt2c-v1 protein was detected in the apical membrane in opossum kidney cells. The expression of Npt2c-v1 mRNA was detected in the heart, spleen, testis, uterus, placenta, femur, cerebellum, hippocampus, diencephalon and brain stem of mouse. Using mouse bone primary cultured cells, we showed the expression of Npt2c-v1 mRNA. In addition, the Npt2c protein was detected in the spermatozoa head. Thus, Npt2c-v1 was expressed in extra-renal tissues such as epididymal spermatozoa and may function as a sodium-dependent phosphate transporter.","ja":"Mutations in the SLC34A3 gene, a sodium-dependent inorganic phosphate (Pi) cotransporter, also referred to as NaPi IIc, causes hereditary hypophosphatemic rickets with hypercalciuria (HHRH), an autosomal recessive disorder. In human and rodent, NaPi IIc is mainly localized in the apical membrane of renal proximal tubular cells. In this study, we identified mouse NaPi IIc variant (Npt2c-v1) that lacks the part of the exon 3 sequence that includes the assumed translation initiation site of Npt2c. Microinjection of mouse Npt2c-v1 cRNA into Xenopus oocytes demonstrated that Npt2c-v1 showed sodium-dependent Pi cotransport activity. The characterization of pH dependency showed activation at extracellular alkaline-pH. Furthermore, Npt2c-v1 mediated Pi transport activity was significantly higher at any pH value than those of Npt2c. In an in vitro study, the localization of the Npt2c-v1 protein was detected in the apical membrane in opossum kidney cells. The expression of Npt2c-v1 mRNA was detected in the heart, spleen, testis, uterus, placenta, femur, cerebellum, hippocampus, diencephalon and brain stem of mouse. Using mouse bone primary cultured cells, we showed the expression of Npt2c-v1 mRNA. In addition, the Npt2c protein was detected in the spermatozoa head. Thus, Npt2c-v1 was expressed in extra-renal tissues such as epididymal spermatozoa and may function as a sodium-dependent phosphate transporter."},"publication_date":"2012","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.59","number":"No.1-2","starting_page":"116","ending_page":"126","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.59.116"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22159077","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=254140","label":"url"}],"paper_title":{"en":"Processing and stability of type IIc sodium-dependent phosphate cotransporter mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria.","ja":"Processing and stability of type IIc sodium-dependent phosphate cotransporter mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria."},"authors":{"en":[{"name":"Haito-Sugino Sakiko"},{"name":"Ito Mikiko"},{"name":"Ohi Akiko"},{"name":"Shiozaki Yuji"},{"name":"Kangawa Natsumi"},{"name":"Nishiyama Takashi"},{"name":"Aranami Fumito"},{"name":"Sasaki Shohei"},{"name":"Mori Ayaka"},{"name":"Kido Shinsuke"},{"name":"Tatsumi Sawako"},{"name":"Segawa Hiroko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Haito-Sugino Sakiko"},{"name":"伊藤 美紀子"},{"name":"Ohi Akiko"},{"name":"Shiozaki Yuji"},{"name":"寒川 奈津美"},{"name":"Nishiyama Takashi"},{"name":"Aranami Fumito"},{"name":"Sasaki Shohei"},{"name":"Mori Ayaka"},{"name":"木戸 慎介"},{"name":"辰巳 佐和子"},{"name":"瀬川 博子"},{"name":"宮本 賢一"}]},"description":{"en":"Mutations in the apically located Na(+)-dependent phosphate (NaPi) cotransporter, SLC34A3 (NaPi-IIc), are a cause of hereditary hypophosphatemic rickets with hypercalciuria (HHRH). We have characterized the impact of several HHRH mutations on the processing and stability of human NaPi-IIc. Mutations S138F, G196R, R468W, R564C, and c.228delC in human NaPi-IIc significantly decreased the levels of NaPi cotransport activities in Xenopus oocytes. In S138F and R564C mutant proteins, this reduction is a result of a decrease in the V(max) for P(i), but not the K(m). G196R, R468W, and c.228delC mutants were not localized to oocyte membranes. In opossum kidney (OK) cells, cell surface labeling, microscopic confocal imaging, and pulse-chase experiments showed that G196R and R468W mutations resulted in an absence of cell surface expression owing to endoplasmic reticulum (ER) retention. G196R and R468W mutants could be partially stabilized by low temperature. In blue native-polyacrylamide gel electrophoresis analysis, G196R and R468W mutants were either denatured or present in an aggregation complex. In contrast, S138F and R564C mutants were trafficked to the cell surface, but more rapidly degraded than WT protein. The c.228delC mutant did not affect endogenous NaPi uptake in OK cells. Thus, G196R and R468W mutations cause ER retention, while S138F and R564C mutations stimulate degradation of human NaPi-IIc in renal epithelial cells. Together, these data suggest that the NaPi-IIc mutants in HHRH show defective processing and stability.","ja":"Mutations in the apically located Na(+)-dependent phosphate (NaPi) cotransporter, SLC34A3 (NaPi-IIc), are a cause of hereditary hypophosphatemic rickets with hypercalciuria (HHRH). We have characterized the impact of several HHRH mutations on the processing and stability of human NaPi-IIc. Mutations S138F, G196R, R468W, R564C, and c.228delC in human NaPi-IIc significantly decreased the levels of NaPi cotransport activities in Xenopus oocytes. In S138F and R564C mutant proteins, this reduction is a result of a decrease in the V(max) for P(i), but not the K(m). G196R, R468W, and c.228delC mutants were not localized to oocyte membranes. In opossum kidney (OK) cells, cell surface labeling, microscopic confocal imaging, and pulse-chase experiments showed that G196R and R468W mutations resulted in an absence of cell surface expression owing to endoplasmic reticulum (ER) retention. G196R and R468W mutants could be partially stabilized by low temperature. In blue native-polyacrylamide gel electrophoresis analysis, G196R and R468W mutants were either denatured or present in an aggregation complex. In contrast, S138F and R564C mutants were trafficked to the cell surface, but more rapidly degraded than WT protein. The c.228delC mutant did not affect endogenous NaPi uptake in OK cells. Thus, G196R and R468W mutations cause ER retention, while S138F and R564C mutations stimulate degradation of human NaPi-IIc in renal epithelial cells. Together, these data suggest that the NaPi-IIc mutants in HHRH show defective processing and stability."},"publication_date":"2011-12-07","publication_name":{"en":"American Journal of Physiology, Cell Physiology","ja":"American Journal of Physiology, Cell Physiology"},"volume":"Vol.302","number":"No.9","starting_page":"C1316","ending_page":"30","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajpcell.00314.2011"],"issn":["1522-1563"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/22133837","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84857067805&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=254142","label":"url"}],"paper_title":{"en":"[Calcium pros and cons significance and risk of phosphorus supplementation. The risk of dietary phosphorus intake].","ja":"[Calcium pros and cons significance and risk of phosphorus supplementation. The risk of dietary phosphorus intake]."},"authors":{"en":[{"name":"Ohi Akiko"},{"name":"Nomura Kengo"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Ohi Akiko"},{"name":"Nomura Kengo"},{"name":"宮本 賢一"}]},"description":{"en":"Dietary intake of phosphorus (Pi) is an important determinant of Pi balance in patients who have chronic kidney disease (CKD) and a reduced GFR. High dietary Pi burden may promote vascular calcification and cardiovascular events. Recently, Ohnishi and Razzaque suggest that phosphate toxicity accelerates the mammalian aging process and that reducing the phosphate burden can delay the aging (FASEB J 24, 3562, 2010) . Dietary Pi is derived largely from foods with high protein content or food additives. Accurate information on the Pi content of foods is needed to achieve a low Pi intake and effectively manage CKD and the aging. In this review, we discuss the risk of dietary Pi intake in CKD and the aging.","ja":"Dietary intake of phosphorus (Pi) is an important determinant of Pi balance in patients who have chronic kidney disease (CKD) and a reduced GFR. High dietary Pi burden may promote vascular calcification and cardiovascular events. Recently, Ohnishi and Razzaque suggest that phosphate toxicity accelerates the mammalian aging process and that reducing the phosphate burden can delay the aging (FASEB J 24, 3562, 2010) . Dietary Pi is derived largely from foods with high protein content or food additives. Accurate information on the Pi content of foods is needed to achieve a low Pi intake and effectively manage CKD and the aging. In this review, we discuss the risk of dietary Pi intake in CKD and the aging."},"publication_date":"2011-12","publication_name":{"en":"Clinical Calcium","ja":"Clinical Calcium"},"volume":"Vol.21","number":"No.12","starting_page":"171","ending_page":"174","languages":["eng"],"referee":true,"identifiers":{"issn":["0917-5857"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21816756","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=291143","label":"url"}],"paper_title":{"en":"Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b+/- mice.","ja":"Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b+/- mice."},"authors":{"en":[{"name":"Ohi Akiko"},{"name":"Hanabusa Etsuyo"},{"name":"Ueda Otoya"},{"name":"Segawa Hiroko"},{"name":"Horiba Naoshi"},{"name":"Kaneko Ichiro"},{"name":"Kuwahara Shoji"},{"name":"Mukai Tomo"},{"name":"Sasaki Shohei"},{"name":"Tominaga Rieko"},{"name":"Furutani Junya"},{"name":"Aranami Fumito"},{"name":"Ohtomo Shuichi"},{"name":"Oikawa Yumiko"},{"name":"Kawase Yousuke"},{"name":"Wada Naoko A"},{"name":"Tachibe Takanori"},{"name":"Kakefuda Mami"},{"name":"Tateishi Hiromi"},{"name":"Matsumoto Kaoru"},{"name":"Tatsumi Sawako"},{"name":"Kido Shinsuke"},{"name":"Fukushima Naoshi"},{"name":"Jishage Kou-Ichi"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Ohi Akiko"},{"name":"Hanabusa Etsuyo"},{"name":"Ueda Otoya"},{"name":"瀬川 博子"},{"name":"Horiba Naoshi"},{"name":"金子 一郎"},{"name":"Kuwahara Shoji"},{"name":"Mukai Tomo"},{"name":"Sasaki Shohei"},{"name":"Tominaga Rieko"},{"name":"Furutani Junya"},{"name":"Aranami Fumito"},{"name":"Ohtomo Shuichi"},{"name":"Oikawa Yumiko"},{"name":"Kawase Yousuke"},{"name":"Wada Naoko A"},{"name":"Tachibe Takanori"},{"name":"Kakefuda Mami"},{"name":"Tateishi Hiromi"},{"name":"Matsumoto Kaoru"},{"name":"辰巳 佐和子"},{"name":"木戸 慎介"},{"name":"Fukushima Naoshi"},{"name":"Jishage Kou-Ichi"},{"name":"宮本 賢一"}]},"description":{"en":"An inorganic phosphate (P(i))-restricted diet is important for patients with chronic kidney disease and patients on hemodialysis. Phosphate binders are essential for preventing hyperphosphatemia and ectopic calcification. The sodium-dependent P(i) (Na/P(i)) transport system is involved in intestinal P(i) absorption and is regulated by several factors. The type II sodium-dependent P(i) transporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports P(i). In the present study, we analyzed the phenotype of Npt2b(-/-) and hetero(+/-) mice. Npt2b(-/-) mice died in utero soon after implantation, indicating that Npt2b is essential for early embryonic development. At 4 wk of age, Npt2b(+/-) mice showed hypophosphatemia and low urinary P(i) excretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)(2)D(3) levels were significantly increased in Npt2b(+/-) mice compared with Npt2b(+/+) mice. Npt2b mRNA levels were reduced to 50% that in Npt2b(+/+) mice. In contrast, renal Npt2a and Npt2c transporter protein levels were significantly increased in Npt2b(+/-) mice. At 20 wk of age, Npt2b(+/-) mice showed hypophosphaturia and reduced Na/P(i) cotransport activity in the distal intestine. Npt2b(+/+) mice with adenine-induced renal failure had hyperphosphatemia and high plasma creatinine levels. Npt2b(+/-) mice treated with adenine had significantly reduced plasma P(i) levels compared with Npt2b(+/+) mice. Intestinal Npt2b protein and Na(+)/P(i) transport activity levels were significantly lower in Npt2b(+/-) mice than in the Npt2b(+/+) mice. The findings of the present studies suggest that Npt2b is an important target for the prevention of hyperphosphatemia.","ja":"An inorganic phosphate (P(i))-restricted diet is important for patients with chronic kidney disease and patients on hemodialysis. Phosphate binders are essential for preventing hyperphosphatemia and ectopic calcification. The sodium-dependent P(i) (Na/P(i)) transport system is involved in intestinal P(i) absorption and is regulated by several factors. The type II sodium-dependent P(i) transporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports P(i). In the present study, we analyzed the phenotype of Npt2b(-/-) and hetero(+/-) mice. Npt2b(-/-) mice died in utero soon after implantation, indicating that Npt2b is essential for early embryonic development. At 4 wk of age, Npt2b(+/-) mice showed hypophosphatemia and low urinary P(i) excretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)(2)D(3) levels were significantly increased in Npt2b(+/-) mice compared with Npt2b(+/+) mice. Npt2b mRNA levels were reduced to 50% that in Npt2b(+/+) mice. In contrast, renal Npt2a and Npt2c transporter protein levels were significantly increased in Npt2b(+/-) mice. At 20 wk of age, Npt2b(+/-) mice showed hypophosphaturia and reduced Na/P(i) cotransport activity in the distal intestine. Npt2b(+/+) mice with adenine-induced renal failure had hyperphosphatemia and high plasma creatinine levels. Npt2b(+/-) mice treated with adenine had significantly reduced plasma P(i) levels compared with Npt2b(+/+) mice. Intestinal Npt2b protein and Na(+)/P(i) transport activity levels were significantly lower in Npt2b(+/-) mice than in the Npt2b(+/+) mice. The findings of the present studies suggest that Npt2b is an important target for the prevention of hyperphosphatemia."},"publication_date":"2011-08-03","publication_name":{"en":"American Journal of Physiology, Renal Physiology","ja":"American Journal of Physiology, Renal Physiology"},"volume":"Vol.301","number":"No.5","starting_page":"F1105","ending_page":"13","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajprenal.00663.2010"],"issn":["1522-1466"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21292849","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=254112","label":"url"}],"paper_title":{"en":"Source matters: from phosphorus load to bioavailability.","ja":"Source matters: from phosphorus load to bioavailability."},"authors":{"en":[{"name":"Fukagawa Masafumi"},{"name":"Komaba Hirotaka"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Fukagawa Masafumi"},{"name":"Komaba Hirotaka"},{"name":"宮本 賢一"}]},"publication_date":"2011-02-03","publication_name":{"en":"Clinical Journal of the American Society of Nephrology : CJASN","ja":"Clinical Journal of the American Society of Nephrology : CJASN"},"volume":"Vol.6","number":"No.2","starting_page":"239","ending_page":"240","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2215/CJN.11051210"],"issn":["1555-905X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/82750","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21372499","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=241403","label":"url"}],"paper_title":{"en":"Analysis of different complexes of type IIa sodium-dependent phosphate transporter in rat renal cortex using blue-native polyacrylamide gel electrophoresis.","ja":"Analysis of different complexes of type IIa sodium-dependent phosphate transporter in rat renal cortex using blue-native polyacrylamide gel electrophoresis."},"authors":{"en":[{"name":"Tanimura Ayako"},{"name":"Yamada Fumiyo"},{"name":"Saito Akihito"},{"name":"Ito Mikiko"},{"name":"Kimura Toru"},{"name":"Anzai Naohiko"},{"name":"Horie Daisuke"},{"name":"Yamamoto Hironori"},{"name":"Miyamoto Ken-ichi"},{"name":"Taketani Yutaka"},{"name":"Takeda Eiji"}],"ja":[{"name":"谷村 綾子"},{"name":"Yamada Fumiyo"},{"name":"Saito Akihito"},{"name":"伊藤 美紀子"},{"name":"Kimura Toru"},{"name":"Anzai Naohiko"},{"name":"Horie Daisuke"},{"name":"山本 浩範"},{"name":"宮本 賢一"},{"name":"竹谷 豊"},{"name":"武田 英二"}]},"description":{"en":"Type IIa sodium-dependent phosphate transporter (NaPi-IIa) can be localized in the apical plasma membrane of renal proximal tubule to carry out a rate-limiting step of phosphate reabsorption. For the apical localization, NaPi-IIa is required to form a macromolecular complex with some adaptor proteins such as Na(+)/H(+) exchanger regulatory factor 1 (NHERF-1) and ezrin. However, the detail of macromolecular complex containing NaPi-IIa in the apical membrane of the renal proximal tubular cells has not been clarified. In this study, we identified at least four different complexes (220, 480, 920, 1,100 kDa) containing NaPi-IIa by using blue-native polyacrylamide gel electrophoresis. Interestingly, LC-MS/MS analysis and immunoprecipitation analysis reveal that megalin is a component of larger complexes (920 and 1,100 kDa). In addition, NaPi-IIa can be heterogeneously co-localized with ezrin and megalin on the apical membrane of renal proximal tubuler cells by fluorescence microscopy analysis. These results suggest that NaPi-IIa can form some different complexes on the apical plasma membrane of renal proximal tubular cells.","ja":"Type IIa sodium-dependent phosphate transporter (NaPi-IIa) can be localized in the apical plasma membrane of renal proximal tubule to carry out a rate-limiting step of phosphate reabsorption. For the apical localization, NaPi-IIa is required to form a macromolecular complex with some adaptor proteins such as Na(+)/H(+) exchanger regulatory factor 1 (NHERF-1) and ezrin. However, the detail of macromolecular complex containing NaPi-IIa in the apical membrane of the renal proximal tubular cells has not been clarified. In this study, we identified at least four different complexes (220, 480, 920, 1,100 kDa) containing NaPi-IIa by using blue-native polyacrylamide gel electrophoresis. Interestingly, LC-MS/MS analysis and immunoprecipitation analysis reveal that megalin is a component of larger complexes (920 and 1,100 kDa). In addition, NaPi-IIa can be heterogeneously co-localized with ezrin and megalin on the apical membrane of renal proximal tubuler cells by fluorescence microscopy analysis. These results suggest that NaPi-IIa can form some different complexes on the apical plasma membrane of renal proximal tubular cells."},"publication_date":"2011-02","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.58","number":"No.1-2","starting_page":"140","ending_page":"147","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.58.140"],"issn":["1349-6867"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20357029","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=291147","label":"url"}],"paper_title":{"en":"Phosphaturic action of fibroblast growth factor 23 in Npt2 null mice","ja":"Phosphaturic action of fibroblast growth factor 23 in Npt2 null mice"},"authors":{"en":[{"name":"Tomoe Yuka"},{"name":"Segawa Hiroko"},{"name":"Shiozawa Kazuyo"},{"name":"Kaneko Ichiro"},{"name":"Tominaga Rieko"},{"name":"Hanabusa Etsuyo"},{"name":"Aranami Fumito"},{"name":"Furutani Junya"},{"name":"Kuwahara Shoji"},{"name":"Tatsumi Sawako"},{"name":"Matsumoto Mitsuru"},{"name":"Ito Mikiko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Tomoe Yuka"},{"name":"Segawa Hiroko"},{"name":"Shiozawa Kazuyo"},{"name":"金子 一郎"},{"name":"Tominaga Rieko"},{"name":"Hanabusa Etsuyo"},{"name":"Aranami Fumito"},{"name":"Furutani Junya"},{"name":"Kuwahara Shoji"},{"name":"Tatsumi Sawako"},{"name":"松本 満"},{"name":"Ito Mikiko"},{"name":"宮本 賢一"}]},"description":{"en":"In the present study, we evaluated the roles of type II and type III sodium-dependent P(i) cotransporters in fibroblast growth factor 23 (FGF23) activity by administering a vector encoding FGF23 with the R179Q mutation (FGF23M) to wild-type (WT) mice, Npt2a knockout (KO) mice, Npt2c KO mice, and Npt2a(-/-)Npt2c(-/-) mice (DKO mice). In Npt2a KO mice, FGF23M induced severe hypophosphatemia and markedly decreased the levels of Npt2c, type III Na-dependent P(i) transporter (PiT2) protein, and renal Na/P(i) transport activity. In contrast, in Npt2c KO mice, FGF23M decreased plasma phosphate levels comparable to those in FGF23M-injected WT mice. In DKO mice with severe hypophosphatemia, FGF23M administration did not induce an additional increase in urinary phosphate excretion. FGF23 administration significantly decreased intestinal Npt2b protein levels in WT mice but had no effect in Npt2a, Npt2c, and DKO mice, despite marked suppression of plasma 1,25(OH)(2)D(3) levels in all the mutant mice. The main findings were as follow: 1) FGF23-dependent phosphaturic activity in Npt2a KO mice is dependent on renal Npt2c and PiT-2 protein; 2) in DKO mice, renal P(i) reabsorption is not further decreased by FGF23M, but renal vitamin D synthesis is suppressed; and 3) downregulation of intestinal Npt2b may be mediated by a factor(s) other than 1,25(OH)(2)D(3). These findings suggest that Npt2a, Npt2c, and PiT-2 are necessary for the phosphaturic activity of FGF23. Thus complementary regulation of Npt2 family proteins may be involved in systemic P(i) homeostasis.","ja":"In the present study, we evaluated the roles of type II and type III sodium-dependent P(i) cotransporters in fibroblast growth factor 23 (FGF23) activity by administering a vector encoding FGF23 with the R179Q mutation (FGF23M) to wild-type (WT) mice, Npt2a knockout (KO) mice, Npt2c KO mice, and Npt2a(-/-)Npt2c(-/-) mice (DKO mice). In Npt2a KO mice, FGF23M induced severe hypophosphatemia and markedly decreased the levels of Npt2c, type III Na-dependent P(i) transporter (PiT2) protein, and renal Na/P(i) transport activity. In contrast, in Npt2c KO mice, FGF23M decreased plasma phosphate levels comparable to those in FGF23M-injected WT mice. In DKO mice with severe hypophosphatemia, FGF23M administration did not induce an additional increase in urinary phosphate excretion. FGF23 administration significantly decreased intestinal Npt2b protein levels in WT mice but had no effect in Npt2a, Npt2c, and DKO mice, despite marked suppression of plasma 1,25(OH)(2)D(3) levels in all the mutant mice. The main findings were as follow: 1) FGF23-dependent phosphaturic activity in Npt2a KO mice is dependent on renal Npt2c and PiT-2 protein; 2) in DKO mice, renal P(i) reabsorption is not further decreased by FGF23M, but renal vitamin D synthesis is suppressed; and 3) downregulation of intestinal Npt2b may be mediated by a factor(s) other than 1,25(OH)(2)D(3). These findings suggest that Npt2a, Npt2c, and PiT-2 are necessary for the phosphaturic activity of FGF23. Thus complementary regulation of Npt2 family proteins may be involved in systemic P(i) homeostasis."},"publication_date":"2010-03","publication_name":{"en":"American Journal of Physiology, Renal Physiology","ja":"American Journal of Physiology, Renal Physiology"},"volume":"Vol.298","number":"No.6","starting_page":"F1341","ending_page":"F1350","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajprenal.00375.2009"],"issn":["1522-1466"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/20088828","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-77950874525&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=233112","label":"url"}],"paper_title":{"en":"Thyroid hormones regulate phosphate homoeostasis through transcriptional control of the renal type IIa sodium-dependent phosphate co-transporter (Npt2a) gene.","ja":"Thyroid hormones regulate phosphate homoeostasis through transcriptional control of the renal type IIa sodium-dependent phosphate co-transporter (Npt2a) gene."},"authors":{"en":[{"name":"Ishiguro Mariko"},{"name":"Yamamoto Hironori"},{"name":"Masuda Masashi"},{"name":"Kozai Mina"},{"name":"Takei Yuichiro"},{"name":"Tanaka Sarasa"},{"name":"Sato Tadatoshi"},{"name":"Segawa Hiroko"},{"name":"Taketani Yutaka"},{"name":"Arai Hidekazu"},{"name":"Miyamoto Ken-ichi"},{"name":"Takeda Eiji"}],"ja":[{"name":"Ishiguro Mariko"},{"name":"山本 浩範"},{"name":"Masuda Masashi"},{"name":"Kozai Mina"},{"name":"Takei Yuichiro"},{"name":"Tanaka Sarasa"},{"name":"Sato Tadatoshi"},{"name":"瀬川 博子"},{"name":"竹谷 豊"},{"name":"新井 英一"},{"name":"宮本 賢一"},{"name":"武田 英二"}]},"description":{"en":"The type IIa renal sodium-dependent phosphate (Na/Pi) co-transporter Npt2a is implicated in the control of serum phosphate levels. It has been demonstrated previously that renal Npt2a protein and its mRNA expression are both up-regulated by the thyroid hormone T3 (3,3',5-tri-iodothyronine) in rats. However, it has never been established whether the induction was mediated by a direct effect of thyroid hormones on the Npt2a promoter. To address the role of Npt2a in T3-dependent regulation of phosphate homoeostasis and to identify the molecular mechanisms by which thyroid hormones modulate Npt2a gene expression, mice were rendered pharmacologically hypo- and hyper-thyroid. Hypothyroid mice showed low levels of serum phosphate and a marked decrease in renal Npt2a protein abundance. Importantly, we also showed that Npt2a-deficient mice had impaired serum phosphate responsiveness to T3 compared with wild-type mice. Promoter analysis with a luciferase assay revealed that the transcriptional activity of a reporter gene containing the Npt2a promoter and intron 1 was dependent upon TRs (thyroid hormone receptors) and specifically increased by T3 in renal cells. Deletion analysis and EMSAs (electrophoretic mobility-shift assays) determined that there were unique TREs (thyroid-hormone-responsive elements) within intron 1 of the Npt2a gene. These results suggest that Npt2a plays a critical role as a T3-target gene, to control phosphate homoeostasis, and that T3 transcriptionally activates the Npt2a gene via TRs in a renal cell-specific manner.","ja":"The type IIa renal sodium-dependent phosphate (Na/Pi) co-transporter Npt2a is implicated in the control of serum phosphate levels. It has been demonstrated previously that renal Npt2a protein and its mRNA expression are both up-regulated by the thyroid hormone T3 (3,3',5-tri-iodothyronine) in rats. However, it has never been established whether the induction was mediated by a direct effect of thyroid hormones on the Npt2a promoter. To address the role of Npt2a in T3-dependent regulation of phosphate homoeostasis and to identify the molecular mechanisms by which thyroid hormones modulate Npt2a gene expression, mice were rendered pharmacologically hypo- and hyper-thyroid. Hypothyroid mice showed low levels of serum phosphate and a marked decrease in renal Npt2a protein abundance. Importantly, we also showed that Npt2a-deficient mice had impaired serum phosphate responsiveness to T3 compared with wild-type mice. Promoter analysis with a luciferase assay revealed that the transcriptional activity of a reporter gene containing the Npt2a promoter and intron 1 was dependent upon TRs (thyroid hormone receptors) and specifically increased by T3 in renal cells. Deletion analysis and EMSAs (electrophoretic mobility-shift assays) determined that there were unique TREs (thyroid-hormone-responsive elements) within intron 1 of the Npt2a gene. These results suggest that Npt2a plays a critical role as a T3-target gene, to control phosphate homoeostasis, and that T3 transcriptionally activates the Npt2a gene via TRs in a renal cell-specific manner."},"publication_date":"2010-03-15","publication_name":{"en":"The Biochemical Journal","ja":"The Biochemical Journal"},"volume":"Vol.427","number":"No.1","starting_page":"161","ending_page":"169","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1042/BJ20090671"],"issn":["1470-8728"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17448744","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162512","label":"url"}],"paper_title":{"en":"Caveolin-1 in extracellular matrix vesicles secreted from osteoblasts.","ja":"Caveolin-1 in extracellular matrix vesicles secreted from osteoblasts."},"authors":{"en":[{"name":"Sawada Naoki"},{"name":"Taketani Yutaka"},{"name":"Amizuka Norio"},{"name":"Ichikawa Masako"},{"name":"Ogawa Chiharu"},{"name":"Nomoto Kaori"},{"name":"Nashiki Kunitaka"},{"name":"Sato Tadatoshi"},{"name":"Arai Hidekazu"},{"name":"Isshiki Masashi"},{"name":"Segawa Hiroko"},{"name":"Yamamoto Hironori"},{"name":"Miyamoto Ken-ichi"},{"name":"Takeda Eiji"}],"ja":[{"name":"Sawada Naoki"},{"name":"竹谷 豊"},{"name":"Amizuka Norio"},{"name":"Ichikawa Masako"},{"name":"Ogawa Chiharu"},{"name":"Nomoto Kaori"},{"name":"Nashiki Kunitaka"},{"name":"Sato Tadatoshi"},{"name":"新井 英一"},{"name":"Isshiki Masashi"},{"name":"瀬川 博子"},{"name":"山本 浩範"},{"name":"宮本 賢一"},{"name":"武田 英二"}]},"description":{"en":"Caveolin-1 is an essential and signature protein of caveolae, which are small invaginations of the plasma membrane enriched in cholesterol and sphingolipids. Although high levels of expression of caveolin-1 have been demonstrated in osteoblasts as well as endothelial cells, fibroblasts, and muscular cells, the role of caveolin-1 in osteoblasts has not been clarified. Here, we show that caveolin-1 is secreted from osteoblasts in the form of matrix vesicles; extracellular vesicles released from the plasma membrane of osteoblasts. In this study, caveolae and matrix vesicles were similarly enriched in cholesterol and sphingomyelin in fractions isolated from mineralizing MC3T3-E1 cells. Interestingly, in the MC3T3-E1 cells caveolin-1 was enriched in the matrix vesicle fraction as well as the caveolar membrane fraction, and the amount of caveolin-1 in the matrix vesicle fraction increased as differentiation progressed. Localization of caveolin-1 in matrix vesicles was also confirmed in murine tibia. Furthermore, overexpression of caveolin-1 enhanced matrix calcification in MC3T3-E1 cells, whereas knockdown of caveolin-1 diminished it. These results suggest that secreted caveolin-1 as a component of matrix vesicles may play an important role in osteoblast calcification.","ja":"Caveolin-1 is an essential and signature protein of caveolae, which are small invaginations of the plasma membrane enriched in cholesterol and sphingolipids. Although high levels of expression of caveolin-1 have been demonstrated in osteoblasts as well as endothelial cells, fibroblasts, and muscular cells, the role of caveolin-1 in osteoblasts has not been clarified. Here, we show that caveolin-1 is secreted from osteoblasts in the form of matrix vesicles; extracellular vesicles released from the plasma membrane of osteoblasts. In this study, caveolae and matrix vesicles were similarly enriched in cholesterol and sphingomyelin in fractions isolated from mineralizing MC3T3-E1 cells. Interestingly, in the MC3T3-E1 cells caveolin-1 was enriched in the matrix vesicle fraction as well as the caveolar membrane fraction, and the amount of caveolin-1 in the matrix vesicle fraction increased as differentiation progressed. Localization of caveolin-1 in matrix vesicles was also confirmed in murine tibia. Furthermore, overexpression of caveolin-1 enhanced matrix calcification in MC3T3-E1 cells, whereas knockdown of caveolin-1 diminished it. These results suggest that secreted caveolin-1 as a component of matrix vesicles may play an important role in osteoblast calcification."},"publication_date":"2007-07","publication_name":{"en":"Bone","ja":"Bone"},"volume":"Vol.41","number":"No.1","starting_page":"52","ending_page":"58","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bone.2007.02.030"],"issn":["8756-3282"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17400199","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=166397","label":"url"}],"paper_title":{"en":"Vitamin A deficiency induces a decrease in EEG delta power during sleep in mice","ja":"Vitamin A deficiency induces a decrease in EEG delta power during sleep in mice"},"authors":{"en":[{"name":"Kitaoka Kazuyoshi"},{"name":"Hattori, Atsushi"},{"name":"Chikahisa Sachiko"},{"name":"Miyamoto Ken-ichi"},{"name":"Nakaya Yutaka"},{"name":"Sei Hiroyoshi"}],"ja":[{"name":"北岡 和義"},{"name":"Hattori, Atsushi"},{"name":"近久 幸子"},{"name":"宮本 賢一"},{"name":"中屋 豊"},{"name":"勢井 宏義"}]},"description":{"en":"Recent report (Maret, S., Franken, P., Dauvilliers, Y., Ghyselinck, N.B., Chambon, P., Tafti, M., 2005. Retinoic acid signaling affects cortical synchrony during sleep. Science 310, 111-113.) has suggested that vitamin A (retinol and its derivatives) is genetically involved in the electroencephalogram (EEG) delta oscillation during sleep. However, this finding has not yet been confirmed by other studies. In this study, we attempted to record the sleep EEG and behavior, and to quantify striatal monoamines in mice fed a vitamin A-deficient (VAD) diet for 4 weeks, in order to clarify the linkage between the delta oscillation and vitamin A. VAD mice demonstrated a significant decrease in the delta power of the EEG. However, 6-h sleep deprivation caused the recovery of the delta power in VAD mice to a level similar to that of the control. VAD also caused the decrease of spontaneous activity throughout 24-h period. Furthermore, dihydroxyphenylacetic acid, a metabolite of dopamine, was decreased significantly in the striatal tissue of VAD mice. Our present results suggest that the deficiency of vitamin A causes the attenuation of delta power in NREM sleep and spontaneous activity. These attenuations may be related to the alteration of striatal dopaminergic function.","ja":"Recent report (Maret, S., Franken, P., Dauvilliers, Y., Ghyselinck, N.B., Chambon, P., Tafti, M., 2005. Retinoic acid signaling affects cortical synchrony during sleep. Science 310, 111-113.) has suggested that vitamin A (retinol and its derivatives) is genetically involved in the electroencephalogram (EEG) delta oscillation during sleep. However, this finding has not yet been confirmed by other studies. In this study, we attempted to record the sleep EEG and behavior, and to quantify striatal monoamines in mice fed a vitamin A-deficient (VAD) diet for 4 weeks, in order to clarify the linkage between the delta oscillation and vitamin A. VAD mice demonstrated a significant decrease in the delta power of the EEG. However, 6-h sleep deprivation caused the recovery of the delta power in VAD mice to a level similar to that of the control. VAD also caused the decrease of spontaneous activity throughout 24-h period. Furthermore, dihydroxyphenylacetic acid, a metabolite of dopamine, was decreased significantly in the striatal tissue of VAD mice. Our present results suggest that the deficiency of vitamin A causes the attenuation of delta power in NREM sleep and spontaneous activity. These attenuations may be related to the alteration of striatal dopaminergic function."},"publication_date":"2007-03-03","publication_name":{"en":"Brain Research","ja":"Brain Research"},"volume":"Vol.1150","starting_page":"121","ending_page":"130","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.brainres.2007.02.077"],"issn":["0006-8993"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17280725","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=158931","label":"url"}],"paper_title":{"en":"Anxiolytic effect of music depends on ovarian steroid in female mice.","ja":"Anxiolytic effect of music depends on ovarian steroid in female mice."},"authors":{"en":[{"name":"Chikahisa Sachiko"},{"name":"Sano Atsuko"},{"name":"Kitaoka Kazuyoshi"},{"name":"Miyamoto Ken-ichi"},{"name":"Sei Hiroyoshi"}],"ja":[{"name":"近久 幸子"},{"name":"佐野 敦子"},{"name":"北岡 和義"},{"name":"宮本 賢一"},{"name":"勢井 宏義"}]},"description":{"en":"Music is known to be able to elicit emotional changes, including anxiolytic effects. The gonadal steroid hormones estradiol and progesterone have also been reported to play important roles in the modulation of anxiety. In the present study, we examined whether the effect of music on anxiety is related to ovarian steroid in female mice. Behavioral paradigms measuring anxiety were tested in gonadally intact (SHAM) and ovariectomized (OVX) female mice chronically treated with either placebo (OVX/Placebo), 17β-estradiol (OVX/E), or progesterone (OVX/P). In the elevated plus maze, light-dark transition, and marble burying tests, SHAM and OVX/P mice exposed to music showed less anxiety than those exposed to white noise or silence while OVX/placebo mice did not show these effects at all. OVX/E mice showed the anxiolytic effect of music only in the marble burying test. Furthermore, pretreatment with progesterone's metabolite inhibitor completely prevented the anxiolytic effect of music in behavioral tests, while pretreatment with a progesterone receptor blocker did not prevent the anxiolytic effect of music. These results suggest that exposure to music reduces anxiety levels, and ovarian steroids, mainly progesterone, may be involved in the anxiolytic effect of music observed in female mice.","ja":"Music is known to be able to elicit emotional changes, including anxiolytic effects. The gonadal steroid hormones estradiol and progesterone have also been reported to play important roles in the modulation of anxiety. In the present study, we examined whether the effect of music on anxiety is related to ovarian steroid in female mice. Behavioral paradigms measuring anxiety were tested in gonadally intact (SHAM) and ovariectomized (OVX) female mice chronically treated with either placebo (OVX/Placebo), 17β-estradiol (OVX/E), or progesterone (OVX/P). In the elevated plus maze, light-dark transition, and marble burying tests, SHAM and OVX/P mice exposed to music showed less anxiety than those exposed to white noise or silence while OVX/placebo mice did not show these effects at all. OVX/E mice showed the anxiolytic effect of music only in the marble burying test. Furthermore, pretreatment with progesterone's metabolite inhibitor completely prevented the anxiolytic effect of music in behavioral tests, while pretreatment with a progesterone receptor blocker did not prevent the anxiolytic effect of music. These results suggest that exposure to music reduces anxiety levels, and ovarian steroids, mainly progesterone, may be involved in the anxiolytic effect of music observed in female mice."},"publication_date":"2007-01-16","publication_name":{"en":"Behavioural Brain Research","ja":"Behavioural Brain Research"},"volume":"Vol.179","number":"No.1","starting_page":"50","ending_page":"59","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbr.2007.01.010"],"issn":["0166-4328"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/17097861","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=163085","label":"url"}],"paper_title":{"en":"Characterization of the molecular mechanisms involved in the increased insulin secretion in rats with acute liver failure.","ja":"Characterization of the molecular mechanisms involved in the increased insulin secretion in rats with acute liver failure."},"authors":{"en":[{"name":"Kuwahata Masashi"},{"name":"Tomoe Y"},{"name":"Harada Nagakatsu"},{"name":"Amano S"},{"name":"Segawa Hiroko"},{"name":"Tatsumi S"},{"name":"Ito Mikiko"},{"name":"Oka T"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"桑波田 雅士"},{"name":"Tomoe Y"},{"name":"原田 永勝"},{"name":"Amano S"},{"name":"瀬川 博子"},{"name":"Tatsumi S"},{"name":"伊藤 美紀子"},{"name":"Oka T"},{"name":"宮本 賢一"}]},"description":{"en":"To investigate the mechanism of hyperinsulinaemia in rats with acute liver failure induced by the administration of d-galactosamine (GalN), we focused on the role of polyprimidine tract-binding protein (PTB) in islet insulin synthesis. Recent reports indicate that PTB binds and stabilizes mRNA encoding insulin and insulin secretory granule proteins, including islet cell autoantigen 512 (ICA512), prohormone convertase 1/3 (PC1/3), and PC2. In the present study, glucose-stimulated insulin secretion was significantly increased in GalN-treated rats compared to controls. Levels of mRNA encoding insulin 1, ICA512, and PC1/3 were increased in the pancreatic islets of GalN-treated rats. This mRNA level elevation was not prevented by pretreatment with actinomycin D. When the PTB-binding site in insulin 1 mRNA was incubated with the islet cytosolic fraction, the RNA-protein complex level was increased in the cytosolic fraction obtained from GalN-treated rats compared to the level in control rats. The cytosolic fraction obtained from pancreatic islets obtained from GalN-treated rats had an increased PTB level compared to the levels obtained from the pancreatic islets of control rats. These findings suggest that, in rats with acute liver failure, cytosolic PTB binds and stabilizes mRNA encoding insulin and its secretory granule proteins.","ja":"To investigate the mechanism of hyperinsulinaemia in rats with acute liver failure induced by the administration of d-galactosamine (GalN), we focused on the role of polyprimidine tract-binding protein (PTB) in islet insulin synthesis. Recent reports indicate that PTB binds and stabilizes mRNA encoding insulin and insulin secretory granule proteins, including islet cell autoantigen 512 (ICA512), prohormone convertase 1/3 (PC1/3), and PC2. In the present study, glucose-stimulated insulin secretion was significantly increased in GalN-treated rats compared to controls. Levels of mRNA encoding insulin 1, ICA512, and PC1/3 were increased in the pancreatic islets of GalN-treated rats. This mRNA level elevation was not prevented by pretreatment with actinomycin D. When the PTB-binding site in insulin 1 mRNA was incubated with the islet cytosolic fraction, the RNA-protein complex level was increased in the cytosolic fraction obtained from GalN-treated rats compared to the level in control rats. The cytosolic fraction obtained from pancreatic islets obtained from GalN-treated rats had an increased PTB level compared to the levels obtained from the pancreatic islets of control rats. These findings suggest that, in rats with acute liver failure, cytosolic PTB binds and stabilizes mRNA encoding insulin and its secretory granule proteins."},"publication_date":"2007-01","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease","ja":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"},"volume":"Vol.1772","number":"No.1","starting_page":"60","ending_page":"65","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbadis.2006.10.001"],"issn":["0925-4439"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16985216","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162537","label":"url"}],"paper_title":{"en":"Parathyroid hormone-dependent endocytosis of renal type IIc Na-Pi cotransporter.","ja":"Parathyroid hormone-dependent endocytosis of renal type IIc Na-Pi cotransporter."},"authors":{"en":[{"name":"Segawa Hiroko"},{"name":"Yamanaka Setsuko"},{"name":"Onitsuka Akemi"},{"name":"Tomoe Yuka"},{"name":"Kuwahata Masashi"},{"name":"Ito Mikiko"},{"name":"Taketani Yutaka"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"瀬川 博子"},{"name":"Yamanaka Setsuko"},{"name":"Onitsuka Akemi"},{"name":"Tomoe Yuka"},{"name":"桑波田 雅士"},{"name":"伊藤 美紀子"},{"name":"竹谷 豊"},{"name":"宮本 賢一"}]},"description":{"en":"Hereditary hypophosphatemic rickets with hypercalciuria results from mutations of the renal type IIc Na-P(i) cotransporter gene, suggesting that the type IIc transporter plays a prominent role in renal phosphate handling. The goal of the present study was to investigate the regulation of the type IIc Na-P(i) cotransporter by parathyroid hormone (PTH). Type IIc Na-P(i) cotransporter levels were markedly increased in thyroparathyroidectomized (TPTX) rats. Four hours after administration of PTH, type IIc transporter protein levels were markedly decreased in the apical membrane fraction but recovered to baseline levels at 24 h. Immunohistochemical analyses demonstrated the presence of the type IIc transporter in the apical membrane and subapical compartments in the proximal tubular cells in TPTX animals. After administration of PTH, the intensity of immunoreactive signals in apical and subapical type IIc transporter decreased in the renal proximal tubular cells in TPTX rats. Colchicine completely blocked the internalization of the type IIc transporter. In addition, leupeptin prevented the PTH-mediated degradation of the type IIa transporter in lysosomes but had no effect on PTH-mediated degradation of the lysosomal type IIc transporter. In PTH-treated TPTX rats, the internalization of the type IIc transporter occurred after administration of PTH(1-34) (PKA and PKC activator) or PTH(3-34) (PKC activator). Thus the present study demonstrated that PTH is a major hormonal regulator of the type IIc Na-P(i) cotransporter in renal proximal tubules.","ja":"Hereditary hypophosphatemic rickets with hypercalciuria results from mutations of the renal type IIc Na-P(i) cotransporter gene, suggesting that the type IIc transporter plays a prominent role in renal phosphate handling. The goal of the present study was to investigate the regulation of the type IIc Na-P(i) cotransporter by parathyroid hormone (PTH). Type IIc Na-P(i) cotransporter levels were markedly increased in thyroparathyroidectomized (TPTX) rats. Four hours after administration of PTH, type IIc transporter protein levels were markedly decreased in the apical membrane fraction but recovered to baseline levels at 24 h. Immunohistochemical analyses demonstrated the presence of the type IIc transporter in the apical membrane and subapical compartments in the proximal tubular cells in TPTX animals. After administration of PTH, the intensity of immunoreactive signals in apical and subapical type IIc transporter decreased in the renal proximal tubular cells in TPTX rats. Colchicine completely blocked the internalization of the type IIc transporter. In addition, leupeptin prevented the PTH-mediated degradation of the type IIa transporter in lysosomes but had no effect on PTH-mediated degradation of the lysosomal type IIc transporter. In PTH-treated TPTX rats, the internalization of the type IIc transporter occurred after administration of PTH(1-34) (PKA and PKC activator) or PTH(3-34) (PKC activator). Thus the present study demonstrated that PTH is a major hormonal regulator of the type IIc Na-P(i) cotransporter in renal proximal tubules."},"publication_date":"2007-01","publication_name":{"en":"American Journal of Physiology, Renal Physiology","ja":"American Journal of Physiology, Renal Physiology"},"volume":"Vol.292","number":"No.1","starting_page":"F395","ending_page":"F403","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajprenal.00100.2006"],"issn":["1931-857X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/40015161008/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1520291855700655232/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162018","label":"url"}],"paper_title":{"en":"リンとビタミンDの相互作用","ja":"リンとビタミンDの相互作用"},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"Segawa Hiroko"},{"name":"Ito Mikiko"},{"name":"辰巳 佐和子"},{"name":"Taketani Yutaka"}],"ja":[{"name":"宮本 賢一"},{"name":"瀬川 博子"},{"name":"伊藤 美紀子"},{"name":"辰巳 佐和子"},{"name":"竹谷 豊"}]},"publication_date":"2006-11","publication_name":{"en":"Orthopeadics and Traumatology","ja":"整形・災害外科"},"volume":"Vol.49","number":"No.12","starting_page":"1365","ending_page":"1370","languages":["jpn"],"referee":true,"identifiers":{"issn":["0387-4095"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16523877","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162006","label":"url"}],"paper_title":{"en":"Molecular mechanism in biological transport in the kidney: Sodium-dependent glucose, phosphate, amino acid transporters.","ja":"Molecular mechanism in biological transport in the kidney: Sodium-dependent glucose, phosphate, amino acid transporters."},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"Ito Mikiko"},{"name":"Segawa Hiroko"},{"name":"Kuwahata Masashi"}],"ja":[{"name":"宮本 賢一"},{"name":"伊藤 美紀子"},{"name":"瀬川 博子"},{"name":"桑波田 雅士"}]},"publication_date":"2006-02","publication_name":{"en":"Nihon Rinsho. Japanese Journal of Clinical Medicine","ja":"Nihon Rinsho. Japanese Journal of Clinical Medicine"},"volume":"Vol.64","starting_page":"145","ending_page":"149","languages":["eng"],"referee":true,"identifiers":{"issn":["0047-1852"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162007","label":"url"}],"paper_title":{"en":"FGF23","ja":"FGF23"},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"Segawa Hiroko"}],"ja":[{"name":"宮本 賢一"},{"name":"瀬川 博子"}]},"publication_date":"2006-01","publication_name":{"en":"Journal of Clinical and Experimental Medicine","ja":"医学のあゆみ"},"volume":"Vol.216","number":"No.2","starting_page":"185","ending_page":"186","languages":["jpn"],"referee":true,"identifiers":{"issn":["0039-2359"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://cir.nii.ac.jp/crid/1020000781987488265/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162019","label":"url"}],"paper_title":{"en":"栄養素の代謝と生理機能","ja":"栄養素の代謝と生理機能"},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"Segawa Hiroko"},{"name":"Ito Mikiko"},{"name":"辰巳 佐和子"},{"name":"Taketani Yutaka"}],"ja":[{"name":"宮本 賢一"},{"name":"瀬川 博子"},{"name":"伊藤 美紀子"},{"name":"辰巳 佐和子"},{"name":"竹谷 豊"}]},"publication_date":"2006","publication_name":{"en":"病態栄養専門師のための病態栄養ガイドブック","ja":"病態栄養専門師のための病態栄養ガイドブック"},"starting_page":"14","ending_page":"19","languages":["jpn"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://id.ndl.go.jp/bib/8031230","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1521417754909593088/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162017","label":"url"}],"paper_title":{"en":"リン制限は糖代謝を制御して寿命を延長させる","ja":"リン制限は糖代謝を制御して寿命を延長させる"},"authors":{"en":[{"name":"Ito Mikiko"},{"name":"拝藤 紗貴子"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"伊藤 美紀子"},{"name":"拝藤 紗貴子"},{"name":"宮本 賢一"}]},"publication_date":"2006","publication_name":{"en":"食品工業","ja":"食品工業"},"volume":"Vol.49","number":"No.18","starting_page":"44","ending_page":"51","languages":["jpn"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://search.jamas.or.jp/link/ui/2007007195","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1010282256960838282/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162016","label":"url"}],"paper_title":{"en":"リン酸トランスポーターをめぐる最近の話題","ja":"リン酸トランスポーターをめぐる最近の話題"},"authors":{"en":[{"name":"Segawa Hiroko"},{"name":"塩澤 和代"},{"name":"鬼塚 朱美"},{"name":"荒波 史"},{"name":"古谷 順也"},{"name":"Ito Mikiko"},{"name":"Kuwahata Masashi"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"瀬川 博子"},{"name":"塩澤 和代"},{"name":"鬼塚 朱美"},{"name":"荒波 史"},{"name":"古谷 順也"},{"name":"伊藤 美紀子"},{"name":"桑波田 雅士"},{"name":"宮本 賢一"}]},"publication_date":"2006","publication_name":{"en":"腎と透析","ja":"腎と透析"},"volume":"Vol.61","number":"No.1","starting_page":"125","ending_page":"130","languages":["jpn"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://cir.nii.ac.jp/crid/1010282256960838281/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162015","label":"url"}],"paper_title":{"en":"Neutral endopeptidase family of protein.","ja":"Neutral endopeptidase family of protein."},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"Ito Mikiko"}],"ja":[{"name":"宮本 賢一"},{"name":"伊藤 美紀子"}]},"publication_date":"2006","publication_name":{"en":"Kidney and Dialysis","ja":"腎と透析"},"volume":"Vol.60","number":"No.4","starting_page":"546","ending_page":"548","languages":["jpn"],"referee":true,"identifiers":{"issn":["0385-2156"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162010","label":"url"}],"paper_title":{"en":"ナトリウム・グルコース,ナトリウム・リン,ナトリウム・アミノ酸共役トランスポーター","ja":"ナトリウム・グルコース,ナトリウム・リン,ナトリウム・アミノ酸共役トランスポーター"},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"Ito Mikiko"},{"name":"Segawa Hiroko"},{"name":"Kuwahata Masashi"}],"ja":[{"name":"宮本 賢一"},{"name":"伊藤 美紀子"},{"name":"瀬川 博子"},{"name":"桑波田 雅士"}]},"publication_date":"2006","publication_name":{"en":"Nihon Rinsho. Japanese Journal of Clinical Medicine","ja":"日本臨牀"},"volume":"Vol.64","number":"No.2","starting_page":"145","ending_page":"149","languages":["jpn"],"referee":true,"identifiers":{"issn":["0047-1852"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://cir.nii.ac.jp/crid/1020000781987488258/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162009","label":"url"}],"paper_title":{"en":"ナトリウム依存症リントランスポータ-の調節機構","ja":"ナトリウム依存症リントランスポータ-の調節機構"},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"Taketani Yutaka"},{"name":"Ito Mikiko"},{"name":"Segawa Hiroko"}],"ja":[{"name":"宮本 賢一"},{"name":"竹谷 豊"},{"name":"伊藤 美紀子"},{"name":"瀬川 博子"}]},"publication_date":"2006","publication_name":{"en":"Annual Review 腎臓","ja":"Annual Review 腎臓"},"starting_page":"216","ending_page":"220","languages":["jpn"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://cir.nii.ac.jp/crid/1020000781987488257/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=162008","label":"url"}],"paper_title":{"en":"生体内におけるリンの役割 --- 光と影","ja":"生体内におけるリンの役割 --- 光と影"},"authors":{"en":[{"name":"Segawa Hiroko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"瀬川 博子"},{"name":"宮本 賢一"}]},"publication_date":"2006","publication_name":{"en":"Kidney and Dialysis","ja":"腎と透析"},"volume":"Vol.60","number":"No.1","starting_page":"36","ending_page":"41","languages":["jpn"],"referee":true,"identifiers":{"issn":["0385-2156"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16380173","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=147667","label":"url"}],"paper_title":{"en":"Alternative promoters and renal cell-specific regulation of the mouse type IIa sodium-dependent phosphate cotransporter gene","ja":"Alternative promoters and renal cell-specific regulation of the mouse type IIa sodium-dependent phosphate cotransporter gene"},"authors":{"en":[{"name":"Yamamoto Hironori"},{"name":"Tani Yoshiko"},{"name":"Kobayashi Kumi"},{"name":"Taketani Yutaka"},{"name":"Sato Tadatoshi"},{"name":"Arai Hidekazu"},{"name":"Morita Kyoko"},{"name":"Miyamoto Ken-ichi"},{"name":"Pike Wesley John"},{"name":"Kato Shigeaki"},{"name":"Takeda Eiji"}],"ja":[{"name":"山本 浩範"},{"name":"Tani Yoshiko"},{"name":"Kobayashi Kumi"},{"name":"竹谷 豊"},{"name":"Sato Tadatoshi"},{"name":"新井 英一"},{"name":"森田 恭子"},{"name":"宮本 賢一"},{"name":"Pike Wesley John"},{"name":"Kato Shigeaki"},{"name":"武田 英二"}]},"description":{"en":"The type IIa sodium-dependent phosphate cotransporter (NPT2a) expressed in renal proximal tubules represents an important determinant in maintaining inorganic phosphate (Pi) homeostasis. In the present study, we identified two variant transcripts of the mouse NPT2a gene, Npt2a-v1 and Npt2a-v2, characterized by the presence of alternative first exons (either exon 1A or exon 1B). The chromosomal structure analysis revealed that the Npt2a gene comprises of two promoters (promoters 1 and 2) and 14 exons, and spans approximately 17 kb. Quantitative PCR analysis showed that renal mRNA levels of both the variants markedly decreased in X-linked vitamin D-resistant hypophosphatemic rickets (Hyp) mice compared to normal littermates. Interestingly, transcriptional activity of a reporter gene, containing Npt2a promoters 1 and 2, was renal cell-specifically increased by 1alpha, 25(OH)2D3 and its analogs. The deletion analysis revealed that the CAAT box in the Npt2a promoter 2 is important for the 1alpha, 25(OH)2D3-dependent renal cell-specific activation of the reporter gene. These data suggested that two alternative promoters control the renal expression of Npt2a gene and both Npt2a variant transcripts are down regulated in Hyp mice.","ja":"The type IIa sodium-dependent phosphate cotransporter (NPT2a) expressed in renal proximal tubules represents an important determinant in maintaining inorganic phosphate (Pi) homeostasis. In the present study, we identified two variant transcripts of the mouse NPT2a gene, Npt2a-v1 and Npt2a-v2, characterized by the presence of alternative first exons (either exon 1A or exon 1B). The chromosomal structure analysis revealed that the Npt2a gene comprises of two promoters (promoters 1 and 2) and 14 exons, and spans approximately 17 kb. Quantitative PCR analysis showed that renal mRNA levels of both the variants markedly decreased in X-linked vitamin D-resistant hypophosphatemic rickets (Hyp) mice compared to normal littermates. Interestingly, transcriptional activity of a reporter gene, containing Npt2a promoters 1 and 2, was renal cell-specifically increased by 1alpha, 25(OH)2D3 and its analogs. The deletion analysis revealed that the CAAT box in the Npt2a promoter 2 is important for the 1alpha, 25(OH)2D3-dependent renal cell-specific activation of the reporter gene. These data suggested that two alternative promoters control the renal expression of Npt2a gene and both Npt2a variant transcripts are down regulated in Hyp mice."},"publication_date":"2005-12-13","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression","ja":"Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression"},"volume":"Vol.1732","number":"No.1-3","starting_page":"43","ending_page":"52","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbaexp.2005.11.003"],"issn":["0167-4781"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16105044","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=147665","label":"url"}],"paper_title":{"en":"Role of membrane microdomains in PTH-mediated down-regulation of NaPi-IIa in opossum kidney cells","ja":"Role of membrane microdomains in PTH-mediated down-regulation of NaPi-IIa in opossum kidney cells"},"authors":{"en":[{"name":"Nashiki Kunitaka"},{"name":"Taketani Yutaka"},{"name":"Takeichi Tomoko"},{"name":"Sawada Naoki"},{"name":"Yamamoto Hironori"},{"name":"Ichikawa Masako"},{"name":"Arai Hidekazu"},{"name":"Miyamoto Ken-ichi"},{"name":"Takeda Eiji"}],"ja":[{"name":"Nashiki Kunitaka"},{"name":"竹谷 豊"},{"name":"Takeichi Tomoko"},{"name":"Sawada Naoki"},{"name":"山本 浩範"},{"name":"Ichikawa Masako"},{"name":"新井 英一"},{"name":"宮本 賢一"},{"name":"武田 英二"}]},"description":{"en":"Parathyroid hormone (PTH) rapidly down-regulates type IIa sodium-dependent phosphate transporter (NaPi-IIa) via an endocytic pathway. Since the relationship between PTH signaling and NaPi-IIa endocytosis has not been explored, we investigated the role of membrane microdomains in this process. We examined the submembrane localization of NaPi-IIa in opossum kidney (OK-N2) cells that stably expressed human NaPi-IIa, and searched for a PTH-induced specific phosphorylating substrate on their membrane microdomains by immunoblotting with specific antibody against phospho substrates of protein kinases. We found that NaPi-IIa was primarily localized in low-density membrane (LDM) domains of the plasma membrane; PTH reduced the levels of immunoreactive NaPi-IIa in these domains. Furthermore, PTH activated both protein kinase A (PKA) and protein kinase Calpha (PKCa) and increased the phosphorylation of 250 kD and 80 kD substrates; this latter substrate was identified as ezrin, which a member of the ezrin-radixin-moesin (ERM) protein family. In response to PTH, ezrin was phosphorylated by both PKA and PKC. Dominant negative ezrin blocked the reduction in NaPi-IIa expression in the LDM domains that was induced by PTH. These data suggest that NaPi-IIa and PTH-induced phosphorylated proteins that include ezrin are compartmentalized in LDM microdomains. This compartmentalization may play an important role in the down-regulation of NaPi-IIa via endocytosis.","ja":"Parathyroid hormone (PTH) rapidly down-regulates type IIa sodium-dependent phosphate transporter (NaPi-IIa) via an endocytic pathway. Since the relationship between PTH signaling and NaPi-IIa endocytosis has not been explored, we investigated the role of membrane microdomains in this process. We examined the submembrane localization of NaPi-IIa in opossum kidney (OK-N2) cells that stably expressed human NaPi-IIa, and searched for a PTH-induced specific phosphorylating substrate on their membrane microdomains by immunoblotting with specific antibody against phospho substrates of protein kinases. We found that NaPi-IIa was primarily localized in low-density membrane (LDM) domains of the plasma membrane; PTH reduced the levels of immunoreactive NaPi-IIa in these domains. Furthermore, PTH activated both protein kinase A (PKA) and protein kinase Calpha (PKCa) and increased the phosphorylation of 250 kD and 80 kD substrates; this latter substrate was identified as ezrin, which a member of the ezrin-radixin-moesin (ERM) protein family. In response to PTH, ezrin was phosphorylated by both PKA and PKC. Dominant negative ezrin blocked the reduction in NaPi-IIa expression in the LDM domains that was induced by PTH. These data suggest that NaPi-IIa and PTH-induced phosphorylated proteins that include ezrin are compartmentalized in LDM microdomains. This compartmentalization may play an important role in the down-regulation of NaPi-IIa via endocytosis."},"publication_date":"2005-09","publication_name":{"en":"Kidney International","ja":"Kidney International"},"volume":"Vol.68","number":"No.3","starting_page":"1137","ending_page":"1147","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/j.1523-1755.2005.00505.x"],"issn":["0085-2538"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15885032","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=291151","label":"url"}],"paper_title":{"en":"Role of the vitamin D receptor in FGF23 action on phosphate metabolism","ja":"Role of the vitamin D receptor in FGF23 action on phosphate metabolism"},"authors":{"en":[{"name":"Inoue Yoshio"},{"name":"Segawa Hiroko"},{"name":"Kaneko Ichiro"},{"name":"Yamanaka Setsuko"},{"name":"Kusano Kenichiro"},{"name":"Kawakami Eri"},{"name":"Furutani Junya"},{"name":"Ito Mikiko"},{"name":"Kuwahata Masashi"},{"name":"Saito Hitoshi"},{"name":"Fukushima Naoshi"},{"name":"Kato Shigeaki"},{"name":"Kanayama Hiro-omi"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Inoue Yoshio"},{"name":"瀬川 博子"},{"name":"金子 一郎"},{"name":"Yamanaka Setsuko"},{"name":"Kusano Kenichiro"},{"name":"Kawakami Eri"},{"name":"Furutani Junya"},{"name":"伊藤 美紀子"},{"name":"桑波田 雅士"},{"name":"Saito Hitoshi"},{"name":"Fukushima Naoshi"},{"name":"Kato Shigeaki"},{"name":"金山 博臣"},{"name":"宮本 賢一"}]},"description":{"en":"FGF23 (fibroblast growth factor 23) is a novel phosphaturic factor that influences vitamin D metabolism and renal re-absorption of Pi. The goal of the present study was to characterize the role of the VDR (vitamin D receptor) in FGF23 action using VDR(-/-) (VDR null) mice. Injection of FGF23M (naked DNA encoding the R179Q mutant of human FGF23) into VDR(-/-) and wildtype VDR(+/+) mice resulted in an elevation in serum FGF23 levels, but had no effect on serum calcium or parathyroid hormone levels. In contrast, injection of FGF23M resulted in significant decreases in serum Pi levels, renal Na/Pi co-transport activity and type II transporter protein levels in both groups when compared with controls injected with mock vector or with FGFWT (naked DNA encoding wild-type human FGF23). Injection of FGF23M resulted in a decrease in 25-hydroxyvitamin D 1a-hydroxylase mRNA levels in VDR(-/-) and VDR(+/+) mice, while 25-hydroxyvitamin D 24-hydroxylase mRNA levels were significantly increased in FGF23M-treated animals compared with mock vector control- or FGF23WT-treated animals. The degree of 24-hydroxylase induction by FGF23M was dependent on the VDR, since FGF23M significantly reduced the levels of serum 1,25(OH)2D3 [1,25-hydroxyvitamin D3] in VDR(+/+) mice, but not in VDR(-/-) mice. We conclude that FGF23 reduces renal Pi transport and 25-hydroxyvitamin D 1a-hydroxylase levels by a mechanism that is independent of the VDR. In contrast, the induction of 25-hydroxyvitamin D 24-hydroxylase and the reduction of serum 1,25(OH)2D3 levels induced by FGF23 are dependent on the VDR.","ja":"FGF23 (fibroblast growth factor 23) is a novel phosphaturic factor that influences vitamin D metabolism and renal re-absorption of Pi. The goal of the present study was to characterize the role of the VDR (vitamin D receptor) in FGF23 action using VDR(-/-) (VDR null) mice. Injection of FGF23M (naked DNA encoding the R179Q mutant of human FGF23) into VDR(-/-) and wildtype VDR(+/+) mice resulted in an elevation in serum FGF23 levels, but had no effect on serum calcium or parathyroid hormone levels. In contrast, injection of FGF23M resulted in significant decreases in serum Pi levels, renal Na/Pi co-transport activity and type II transporter protein levels in both groups when compared with controls injected with mock vector or with FGFWT (naked DNA encoding wild-type human FGF23). Injection of FGF23M resulted in a decrease in 25-hydroxyvitamin D 1a-hydroxylase mRNA levels in VDR(-/-) and VDR(+/+) mice, while 25-hydroxyvitamin D 24-hydroxylase mRNA levels were significantly increased in FGF23M-treated animals compared with mock vector control- or FGF23WT-treated animals. The degree of 24-hydroxylase induction by FGF23M was dependent on the VDR, since FGF23M significantly reduced the levels of serum 1,25(OH)2D3 [1,25-hydroxyvitamin D3] in VDR(+/+) mice, but not in VDR(-/-) mice. We conclude that FGF23 reduces renal Pi transport and 25-hydroxyvitamin D 1a-hydroxylase levels by a mechanism that is independent of the VDR. In contrast, the induction of 25-hydroxyvitamin D 24-hydroxylase and the reduction of serum 1,25(OH)2D3 levels induced by FGF23 are dependent on the VDR."},"publication_date":"2005-08-15","publication_name":{"en":"The Biochemical Journal","ja":"The Biochemical Journal"},"volume":"Vol.390","number":"No.1","starting_page":"325","ending_page":"331","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1042/BJ20041799"],"issn":["1470-8728"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16076377","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=126769","label":"url"}],"paper_title":{"en":"Inhibition of Intestinal Sodium-dependent Inorganic phosphate Transport by Fibroblast Growth Factor 23","ja":"Inhibition of Intestinal Sodium-dependent Inorganic phosphate Transport by Fibroblast Growth Factor 23"},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"Ito Mikiko"},{"name":"Kuwahata Masashi"},{"name":"Kato Shigeaki"},{"name":"Segawa Hiroko"}],"ja":[{"name":"宮本 賢一"},{"name":"伊藤 美紀子"},{"name":"桑波田 雅士"},{"name":"Kato Shigeaki"},{"name":"瀬川 博子"}]},"description":{"en":"The mechanisms by which fibroblast growth factor 23 (FGF23) alters inorganic phosphate (Pi) homeostasis is not entirely clear. In the present study, we examined the effect of FGF23 on intestinal sodium-dependent Pi transport in mice. Injection of FGF23(R179Q) markedly reduced serum Pi and 1,25(OH)2D3 levels in normal mice. Those animals show the reduction of intestinal sodium-dependent Pi transport activity and the amount of type IIb sodium-dependent Pi cotransporter (type IIb NaPi) protein in the brush border membrane vesicles. In vitamin D receptor null mice (VDR-/-), FGF23(R179Q) had no effect on intestinal sodium-dependent Pi transport activity and type IIb NaPi protein levels. The present study suggests that FGF23(R179Q) reduces intestinal sodium-dependent Pi transport activity and type IIb NaPi protein levels by a mechanism that is dependent on VDR.","ja":"The mechanisms by which fibroblast growth factor 23 (FGF23) alters inorganic phosphate (Pi) homeostasis is not entirely clear. In the present study, we examined the effect of FGF23 on intestinal sodium-dependent Pi transport in mice. Injection of FGF23(R179Q) markedly reduced serum Pi and 1,25(OH)2D3 levels in normal mice. Those animals show the reduction of intestinal sodium-dependent Pi transport activity and the amount of type IIb sodium-dependent Pi cotransporter (type IIb NaPi) protein in the brush border membrane vesicles. In vitamin D receptor null mice (VDR-/-), FGF23(R179Q) had no effect on intestinal sodium-dependent Pi transport activity and type IIb NaPi protein levels. The present study suggests that FGF23(R179Q) reduces intestinal sodium-dependent Pi transport activity and type IIb NaPi protein levels by a mechanism that is dependent on VDR."},"publication_date":"2005-08","publication_name":{"en":"Therapeutic Apheresis and Dialysis","ja":"Therapeutic Apheresis and Dialysis"},"volume":"Vol.9","number":"No.4","starting_page":"331","ending_page":"335","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1111/j.1744-9987.2005.00292.x"],"issn":["1744-9979"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15961073","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=126789","label":"url"}],"paper_title":{"en":"Inhibitory effect of JTP-59557, a new triazole derivative, on intestinal phosphate transport in vitro and in vivo","ja":"Inhibitory effect of JTP-59557, a new triazole derivative, on intestinal phosphate transport in vitro and in vivo"},"authors":{"en":[{"name":"Matsuo Akira"},{"name":"Negoro Tamotsu"},{"name":"Seo Tomohisa"},{"name":"Kitao Yuki"},{"name":"Shindo Masanori"},{"name":"Segawa Hiroko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Matsuo Akira"},{"name":"Negoro Tamotsu"},{"name":"Seo Tomohisa"},{"name":"Kitao Yuki"},{"name":"Shindo Masanori"},{"name":"瀬川 博子"},{"name":"宮本 賢一"}]},"description":{"en":"JTP-59557 [(-)-4-(2-tert-Butyl-4,5-dichlorophenyl)-5-(5-trifluoromethylpyridin-2-ylsulfanyl)-4H-[1,2,4]triazol-3-ol] showed an inhibitory effect on Na(+)-dependent inorganic phosphate (Pi) transport in intestinal brush border membrane vesicles with an IC(50) value of 0.40 microM in rabbit and with an IC(50) of 0.19 microM in rat, without affecting Na(+)-independent Pi and Na(+)-dependent d-glucose transport activities. In Chinese hamster ovary (CHO) cells expressing human type IIb Na/Pi cotransporter (type IIb), JTP-59557 decreased human type IIb-mediated Pi uptake with an IC(50) of 0.12 microM. In rabbit intestinal brush border membrane vesicles, JTP-59557 behaved as a noncompetitive inhibitor with respect to Pi. In an in vivo study, single administration of JTP-59557 significantly decreased the intestinal Pi absorption rate, when either Pi solution or laboratory chow was given to rats. In this report, we show that JTP-59557 is a potent, selective, stereospecific, noncompetitive inhibitor of intestinal Na/Pi cotransporters including type IIb, and it may represent a new class of intestinal Pi absorption inhibitor.","ja":"JTP-59557 [(-)-4-(2-tert-Butyl-4,5-dichlorophenyl)-5-(5-trifluoromethylpyridin-2-ylsulfanyl)-4H-[1,2,4]triazol-3-ol] showed an inhibitory effect on Na(+)-dependent inorganic phosphate (Pi) transport in intestinal brush border membrane vesicles with an IC(50) value of 0.40 microM in rabbit and with an IC(50) of 0.19 microM in rat, without affecting Na(+)-independent Pi and Na(+)-dependent d-glucose transport activities. In Chinese hamster ovary (CHO) cells expressing human type IIb Na/Pi cotransporter (type IIb), JTP-59557 decreased human type IIb-mediated Pi uptake with an IC(50) of 0.12 microM. In rabbit intestinal brush border membrane vesicles, JTP-59557 behaved as a noncompetitive inhibitor with respect to Pi. In an in vivo study, single administration of JTP-59557 significantly decreased the intestinal Pi absorption rate, when either Pi solution or laboratory chow was given to rats. In this report, we show that JTP-59557 is a potent, selective, stereospecific, noncompetitive inhibitor of intestinal Na/Pi cotransporters including type IIb, and it may represent a new class of intestinal Pi absorption inhibitor."},"publication_date":"2005-07-04","publication_name":{"en":"European Journal of Pharmacology","ja":"European Journal of Pharmacology"},"volume":"Vol.517","number":"No.1-2","starting_page":"111","ending_page":"119","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.ejphar.2005.05.003"],"issn":["0014-2999"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15671080","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=126777","label":"url"}],"paper_title":{"en":"Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells","ja":"Vitamin D and phosphate regulate fibroblast growth factor-23 in K-562 cells"},"authors":{"en":[{"name":"Ito Mikiko"},{"name":"Sakai Yuko"},{"name":"Furumoto Mari"},{"name":"Segawa Hiroko"},{"name":"Haito Sakiko"},{"name":"Yamanaka Setsuko"},{"name":"Nakamura Rie"},{"name":"Kuwahata Masashi"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"伊藤 美紀子"},{"name":"Sakai Yuko"},{"name":"Furumoto Mari"},{"name":"瀬川 博子"},{"name":"Haito Sakiko"},{"name":"Yamanaka Setsuko"},{"name":"Nakamura Rie"},{"name":"桑波田 雅士"},{"name":"宮本 賢一"}]},"description":{"en":"Fibroblast growth factor-23 (FGF-23) has been recently identified as playing an important pathophysiological role in phosphate homeostasis and vitamin D metabolism. To elucidate the precise physiological regulation of FGF-23, we characterized the mouse FGF-23 5'-flanking region and analyzed its promoter activity. The 5'-flanking region of the mouse FGF-23 gene contained a TFIID site (TATA box) and several putative transcription factor binding sites, including MZF1, GATA-1 and c-Ets-1 motifs, but it did not contain the typical sequences of the vitamin D response element. Plasmids encoding 554-bp (pGL/-0.6), 364-bp (pGL/-0.4) and 200-bp (pGL/-0.13) promoter regions containing the TFIID element and +1-bp fragments drove the downstream expression of a luciferase reporter gene in transfection assays. We also found that FGF-23 mRNA was expressed in K-562 erythroleukemia cell lines but not in MC3T3-E1, Raji, or Hep G2 human carcinoma cells. Treatment with 1,25-dihydroxyvitamin D3 in the presence of high phosphate markedly stimulated pGL/-0.6 activity, but calcium had no effect. In addition, the plasma FGF-23 levels were affected by the dietary and plasma inorganic phosphate concentrations. Finally, the levels of plasma FGF-23 in vitamin D receptor-null mice were significantly lower than in wild-type mice. The presents study demonstrated that vitamin D and the plasma phosphate level are important regulators of the transcription of the mouse FGF-23 gene.","ja":"Fibroblast growth factor-23 (FGF-23) has been recently identified as playing an important pathophysiological role in phosphate homeostasis and vitamin D metabolism. To elucidate the precise physiological regulation of FGF-23, we characterized the mouse FGF-23 5'-flanking region and analyzed its promoter activity. The 5'-flanking region of the mouse FGF-23 gene contained a TFIID site (TATA box) and several putative transcription factor binding sites, including MZF1, GATA-1 and c-Ets-1 motifs, but it did not contain the typical sequences of the vitamin D response element. Plasmids encoding 554-bp (pGL/-0.6), 364-bp (pGL/-0.4) and 200-bp (pGL/-0.13) promoter regions containing the TFIID element and +1-bp fragments drove the downstream expression of a luciferase reporter gene in transfection assays. We also found that FGF-23 mRNA was expressed in K-562 erythroleukemia cell lines but not in MC3T3-E1, Raji, or Hep G2 human carcinoma cells. Treatment with 1,25-dihydroxyvitamin D3 in the presence of high phosphate markedly stimulated pGL/-0.6 activity, but calcium had no effect. In addition, the plasma FGF-23 levels were affected by the dietary and plasma inorganic phosphate concentrations. Finally, the levels of plasma FGF-23 in vitamin D receptor-null mice were significantly lower than in wild-type mice. The presents study demonstrated that vitamin D and the plasma phosphate level are important regulators of the transcription of the mouse FGF-23 gene."},"publication_date":"2005-06","publication_name":{"en":"American Journal of Physiology, Endocrinology and Metabolism","ja":"American Journal of Physiology, Endocrinology and Metabolism"},"volume":"Vol.288","number":"No.6","starting_page":"E1101","ending_page":"E1109","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajpendo.00502.2004"],"issn":["0193-1849"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15601753","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=126797","label":"url"}],"paper_title":{"en":"Characterization of inorganic phosphate transport in osteoclast-like cells","ja":"Characterization of inorganic phosphate transport in osteoclast-like cells"},"authors":{"en":[{"name":"Ito Mikiko"},{"name":"Matsuka Naoko"},{"name":"Izuka Michiyo"},{"name":"Haito Sakiko"},{"name":"Sakai Yuko"},{"name":"Nakamura Rie"},{"name":"Segawa Hiroko"},{"name":"Kuwahata Masashi"},{"name":"Yamamoto Hironori"},{"name":"Pike J Wesley"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"伊藤 美紀子"},{"name":"Matsuka Naoko"},{"name":"Izuka Michiyo"},{"name":"Haito Sakiko"},{"name":"Sakai Yuko"},{"name":"Nakamura Rie"},{"name":"瀬川 博子"},{"name":"桑波田 雅士"},{"name":"山本 浩範"},{"name":"Pike J Wesley"},{"name":"宮本 賢一"}]},"description":{"en":"Osteoclasts possess inorganic phosphate (Pi) transport systems to take up external Pi during bone resorption. In the present study, we characterized Pi transport in mouse osteoclast-like cells that were obtained by differentiation of macrophage RAW264.7 cells with receptor activator of NF-kappaB ligand (RANKL). In undifferentiated RAW264.7 cells, Pi transport into the cells was Na+ dependent, but after treatment with RANKL, Na+-independent Pi transport was significantly increased. In addition, compared with neutral pH, the activity of the Na+-independent Pi transport system in the osteoclast-like cells was markedly enhanced at pH 5.5. The Na+-independent system consisted of two components with Km of 0.35 mM and 7.5 mM. The inhibitors of Pi transport, phosphonoformic acid, and arsenate substantially decreased Pi transport. The proton ionophores nigericin and carbonyl cyanide p-trifluoromethoxyphenylhydrazone as well as a K+ ionophore, valinomycin, significantly suppressed Pi transport activity. Analysis of BCECF fluorescence indicated that Pi transport in osteoclast-like cells is coupled to a proton transport system. In addition, elevation of extracellular K+ ion stimulated Pi transport, suggesting that membrane voltage is involved in the regulation of Pi transport activity. Finally, bone particles significantly increased Na+-independent Pi transport activity in osteoclast-like cells. Thus, osteoclast-like cells have a Pi transport system with characteristics that are different from those of other Na+-dependent Pi transporters. We conclude that stimulation of Pi transport at acidic pH is necessary for bone resorption or for production of the large amounts of energy necessary for acidification of the extracellular environment.","ja":"Osteoclasts possess inorganic phosphate (Pi) transport systems to take up external Pi during bone resorption. In the present study, we characterized Pi transport in mouse osteoclast-like cells that were obtained by differentiation of macrophage RAW264.7 cells with receptor activator of NF-kappaB ligand (RANKL). In undifferentiated RAW264.7 cells, Pi transport into the cells was Na+ dependent, but after treatment with RANKL, Na+-independent Pi transport was significantly increased. In addition, compared with neutral pH, the activity of the Na+-independent Pi transport system in the osteoclast-like cells was markedly enhanced at pH 5.5. The Na+-independent system consisted of two components with Km of 0.35 mM and 7.5 mM. The inhibitors of Pi transport, phosphonoformic acid, and arsenate substantially decreased Pi transport. The proton ionophores nigericin and carbonyl cyanide p-trifluoromethoxyphenylhydrazone as well as a K+ ionophore, valinomycin, significantly suppressed Pi transport activity. Analysis of BCECF fluorescence indicated that Pi transport in osteoclast-like cells is coupled to a proton transport system. In addition, elevation of extracellular K+ ion stimulated Pi transport, suggesting that membrane voltage is involved in the regulation of Pi transport activity. Finally, bone particles significantly increased Na+-independent Pi transport activity in osteoclast-like cells. Thus, osteoclast-like cells have a Pi transport system with characteristics that are different from those of other Na+-dependent Pi transporters. We conclude that stimulation of Pi transport at acidic pH is necessary for bone resorption or for production of the large amounts of energy necessary for acidification of the extracellular environment."},"publication_date":"2005-04","publication_name":{"en":"American Journal of Physiology, Cell Physiology","ja":"American Journal of Physiology, Cell Physiology"},"volume":"Vol.288","number":"No.4","starting_page":"921","ending_page":"931","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajpcell.00412.2004"],"issn":["0363-6143"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15607118","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=130373","label":"url"}],"paper_title":{"en":"Posttranscriptional regulation of albumin gene expression by branched-chain amino acids in rats with acute liver injury","ja":"Posttranscriptional regulation of albumin gene expression by branched-chain amino acids in rats with acute liver injury"},"authors":{"en":[{"name":"Kuwahata Masashi"},{"name":"Kuramoto Yasuko"},{"name":"Tomoe Yuka"},{"name":"Sugata Emi"},{"name":"Segawa Hiroko"},{"name":"Ito Mikiko"},{"name":"Oka Tatsuzo"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"桑波田 雅士"},{"name":"Kuramoto Yasuko"},{"name":"Tomoe Yuka"},{"name":"Sugata Emi"},{"name":"瀬川 博子"},{"name":"伊藤 美紀子"},{"name":"Oka Tatsuzo"},{"name":"宮本 賢一"}]},"description":{"en":"We previously demonstrated that the integration of albumin mRNA into functional polysomes was regulated by the supply of branched-chain amino acids (BCAA) in the liver of galactosamine-treated rats. To study the mechanism of this regulation, we investigated interaction between rat liver proteins and albumin transcripts. When albumin transcript was incubated with ribosome salt wash (RSW) extracts prepared from liver, a specific RNA-protein complex (p65) formed. Competition experiments showed that a pyrimidine-rich sequence in the coding region of albumin mRNA was required for the formation of p65. The level of p65 was increased in the RSW extracts prepared from liver of galactosamine-treated rats infused with a standard amino acid formula, compared with a BCAA-enriched amino acid formula. The protein in p65 appears to be polypyrimidine tract-binding protein (PTB), because the formation of p65 was reduced in the RSW extracts pre-incubated with anti-PTB antibody. In cell-free translation analysis, immunodepletion of PTB from rabbit reticulocyte lysate caused an increase in albumin translation. These results suggest that binding of PTB to albumin mRNA suppresses its translation. A supply of BCAA may interfere with this binding and improve the translation efficiency of albumin mRNA in injured liver.","ja":"We previously demonstrated that the integration of albumin mRNA into functional polysomes was regulated by the supply of branched-chain amino acids (BCAA) in the liver of galactosamine-treated rats. To study the mechanism of this regulation, we investigated interaction between rat liver proteins and albumin transcripts. When albumin transcript was incubated with ribosome salt wash (RSW) extracts prepared from liver, a specific RNA-protein complex (p65) formed. Competition experiments showed that a pyrimidine-rich sequence in the coding region of albumin mRNA was required for the formation of p65. The level of p65 was increased in the RSW extracts prepared from liver of galactosamine-treated rats infused with a standard amino acid formula, compared with a BCAA-enriched amino acid formula. The protein in p65 appears to be polypyrimidine tract-binding protein (PTB), because the formation of p65 was reduced in the RSW extracts pre-incubated with anti-PTB antibody. In cell-free translation analysis, immunodepletion of PTB from rabbit reticulocyte lysate caused an increase in albumin translation. These results suggest that binding of PTB to albumin mRNA suppresses its translation. A supply of BCAA may interfere with this binding and improve the translation efficiency of albumin mRNA in injured liver."},"publication_date":"2004-12-24","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease","ja":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"},"volume":"Vol.1739","number":"No.1","starting_page":"62","ending_page":"69","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/j.bbadis.2004.08.011"],"issn":["0925-4439"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15561978","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=130410","label":"url"}],"paper_title":{"en":"Internalization of renal type IIc Na/Pi cotransporter in response to a high phosphate diet","ja":"Internalization of renal type IIc Na/Pi cotransporter in response to a high phosphate diet"},"authors":{"en":[{"name":"Segawa Hiroko"},{"name":"Yamanaka Setsuko"},{"name":"Ito Mikiko"},{"name":"Kuwahata Masashi"},{"name":"Shono Masayuki"},{"name":"Yamamoto Tadashi"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"瀬川 博子"},{"name":"Yamanaka Setsuko"},{"name":"伊藤 美紀子"},{"name":"桑波田 雅士"},{"name":"庄野 正行"},{"name":"Yamamoto Tadashi"},{"name":"宮本 賢一"}]},"description":{"en":"Dietary phosphate levels regulate the renal brush-border type IIa Na-Pi cotransporter. Another Na-Pi cotransporter, type IIc, colocalizes with type IIa Na-Pi cotransporter in the apical membrane of renal proximal tubular cells. The goal of the present study was to determine whether dietary phosphate levels also rapidly regulate the type IIc Na-Pi cotransporter. Type IIa and type IIc transporter protein levels were increased in rats chronically fed a low-Pi diet compared with those fed a normal-Pi diet. Two hours after beginning a high-Pi diet, type IIa transporter levels were decreased, whereas type IIc protein levels remained unchanged. Western blot analysis of brush-border membrane prepared 4 h after beginning a high-Pi diet showed a significant reduction in type IIc transporter protein levels, and immunohistochemistry showed translocation of the type IIc-immunoreactive signal from the entire brush border to subapical membrane. Membrane fractionation studies revealed a decrease in apical membrane type IIc protein without changes in total cortical type IIc protein, which is compatible with redistribution of type IIc protein from the apical membrane to the dense membrane fraction. The microtubule-disrupting reagent colchicine prevented this reduction in apical type IIc transporter at the apical membrane but had no effect on type IIa transporter levels. These data suggest that the type IIc Na-Pi cotransporter level is rapidly regulated by rapid adaptation to dietary Pi in a microtubule-dependent manner. Furthermore, the mechanisms of the internalization of the type IIc transporter are distinct from those of the type IIa transporter.","ja":"Dietary phosphate levels regulate the renal brush-border type IIa Na-Pi cotransporter. Another Na-Pi cotransporter, type IIc, colocalizes with type IIa Na-Pi cotransporter in the apical membrane of renal proximal tubular cells. The goal of the present study was to determine whether dietary phosphate levels also rapidly regulate the type IIc Na-Pi cotransporter. Type IIa and type IIc transporter protein levels were increased in rats chronically fed a low-Pi diet compared with those fed a normal-Pi diet. Two hours after beginning a high-Pi diet, type IIa transporter levels were decreased, whereas type IIc protein levels remained unchanged. Western blot analysis of brush-border membrane prepared 4 h after beginning a high-Pi diet showed a significant reduction in type IIc transporter protein levels, and immunohistochemistry showed translocation of the type IIc-immunoreactive signal from the entire brush border to subapical membrane. Membrane fractionation studies revealed a decrease in apical membrane type IIc protein without changes in total cortical type IIc protein, which is compatible with redistribution of type IIc protein from the apical membrane to the dense membrane fraction. The microtubule-disrupting reagent colchicine prevented this reduction in apical type IIc transporter at the apical membrane but had no effect on type IIa transporter levels. These data suggest that the type IIc Na-Pi cotransporter level is rapidly regulated by rapid adaptation to dietary Pi in a microtubule-dependent manner. Furthermore, the mechanisms of the internalization of the type IIc transporter are distinct from those of the type IIa transporter."},"publication_date":"2004-11-23","publication_name":{"en":"American Journal of Physiology, Renal Physiology","ja":"American Journal of Physiology, Renal Physiology"},"volume":"Vol.288","number":"No.3","starting_page":"587","ending_page":"596","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajprenal.00097.2004"],"issn":["1931-857X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/110734","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15460899","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-7044220587&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=126805","label":"url"}],"paper_title":{"en":"Stress control and human nutrition","ja":"Stress control and human nutrition"},"authors":{"en":[{"name":"Takeda Eiji"},{"name":"Terao Junji"},{"name":"Nakaya Yutaka"},{"name":"Miyamoto Ken-ichi"},{"name":"Baba Yoshinobu"},{"name":"Chuman Hiroshi"},{"name":"Kaji Ryuji"},{"name":"Ohmori Tetsuro"},{"name":"Rokutan Kazuhito"}],"ja":[{"name":"武田 英二"},{"name":"寺尾 純二"},{"name":"中屋 豊"},{"name":"宮本 賢一"},{"name":"馬場 嘉信"},{"name":"中馬 寛"},{"name":"梶 龍兒"},{"name":"大森 哲郎"},{"name":"六反 一仁"}]},"description":{"en":"Stress is a pervasive factor in everyday life that critically affects development and functioning. Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associated with the onset of depressive illness. Brain food is aimed at preventing as well as treating a growing number of stress-related mental disorders. Some topics on the association of stress and nutrition is reviewed. (1) An increased activity of serotonergic neurons in the brain is an established consequence of stress. An increase in brain tryptophan levels on the order of that produced by eating a carbohydrate-rich/protein-poor meal causes parallel increases in the amounts of serotonin released into synapses. (2) Eating is thought to be suppressed during stress, due to anorectic effects of corticotrophin releasing hormone, and increased during recovery from stress, due to appetite stimulating effects of residual cortisol. (3) A strong inverse association between coffee intake and risk of suicide. (4) Night eating syndrome has been found to occur during periods of stress and is associated with poor results at attempts to lose weight and disturbances in the hypothalamic-pituitary-adrenal axis. (5) Dietary antioxidants present in fruits and vegetables may improve cognitive function. Therefore, it is concluded that the establishment of functional foods that correctly regulate stress response must be firmly based upon scientific knowledge and legal regulation.","ja":"Stress is a pervasive factor in everyday life that critically affects development and functioning. Severe and prolonged stress exposure impairs homeostatic mechanisms, particularly associated with the onset of depressive illness. Brain food is aimed at preventing as well as treating a growing number of stress-related mental disorders. Some topics on the association of stress and nutrition is reviewed. (1) An increased activity of serotonergic neurons in the brain is an established consequence of stress. An increase in brain tryptophan levels on the order of that produced by eating a carbohydrate-rich/protein-poor meal causes parallel increases in the amounts of serotonin released into synapses. (2) Eating is thought to be suppressed during stress, due to anorectic effects of corticotrophin releasing hormone, and increased during recovery from stress, due to appetite stimulating effects of residual cortisol. (3) A strong inverse association between coffee intake and risk of suicide. (4) Night eating syndrome has been found to occur during periods of stress and is associated with poor results at attempts to lose weight and disturbances in the hypothalamic-pituitary-adrenal axis. (5) Dietary antioxidants present in fruits and vegetables may improve cognitive function. Therefore, it is concluded that the establishment of functional foods that correctly regulate stress response must be firmly based upon scientific knowledge and legal regulation."},"publication_date":"2004-08","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.51","number":"No.3-4","starting_page":"139","ending_page":"145","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2152/jmi.51.139"],"issn":["1343-1420"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/15182416","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1390001205043873664/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=126804","label":"url"}],"paper_title":{"en":"Physiological Regulation of Renal Sodium-Dependent Phosphate Cotransporters","ja":"Physiological Regulation of Renal Sodium-Dependent Phosphate Cotransporters"},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"Segawa Hiroko"},{"name":"Ito Mikiko"},{"name":"Kuwahata Masashi"}],"ja":[{"name":"宮本 賢一"},{"name":"瀬川 博子"},{"name":"伊藤 美紀子"},{"name":"桑波田 雅士"}]},"description":{"en":"The physiological regulation of renal Pi reabsorption is mediated by renal type II Na/Pi cotransporters (type IIa and type IIc). The type IIa transporter is regulated, among other factors, by dietary Pi intake and parathyroid hormone (PTH). The PTH-induced inhibition of Pi reabsorption is mediated by endocytosis of the type IIa transporter from the brush-border membrane and subsequent lysosomal degradation. Type IIa is part of the heteromeric protein complexes organized by PDZ proteins. Furthermore, during Pi depletion the type IIc Na/Pi cotransporter is induced in the apical membrane of proximal tubular cells. The type IIc transporter is also regulated by PTH via internalization, but by a vesicular transport pathway distinct from that used by the type IIc transporter. Studying the mechanisms of type IIa and type IIc transporters has increased the understanding of the control of proximal tubular Pi handling and thus of overall Pi homeostasis.","ja":"The physiological regulation of renal Pi reabsorption is mediated by renal type II Na/Pi cotransporters (type IIa and type IIc). The type IIa transporter is regulated, among other factors, by dietary Pi intake and parathyroid hormone (PTH). The PTH-induced inhibition of Pi reabsorption is mediated by endocytosis of the type IIa transporter from the brush-border membrane and subsequent lysosomal degradation. Type IIa is part of the heteromeric protein complexes organized by PDZ proteins. Furthermore, during Pi depletion the type IIc Na/Pi cotransporter is induced in the apical membrane of proximal tubular cells. The type IIc transporter is also regulated by PTH via internalization, but by a vesicular transport pathway distinct from that used by the type IIc transporter. Studying the mechanisms of type IIa and type IIc transporters has increased the understanding of the control of proximal tubular Pi handling and thus of overall Pi homeostasis."},"publication_date":"2004-04","publication_name":{"en":"The Japanese Journal of Physiology","ja":"The Japanese Journal of Physiology"},"volume":"Vol.54","number":"No.2","starting_page":"93","ending_page":"102","languages":["eng"],"referee":true,"identifiers":{"doi":["10.2170/jjphysiol.54.93"],"issn":["0021-521X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/14996670","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=90136","label":"url"}],"paper_title":{"en":"Intestinal Na-Pi cotransporter adaptation to dietary Pi content in vitamin D receptor null mice.","ja":"Intestinal Na-Pi cotransporter adaptation to dietary Pi content in vitamin D receptor null mice."},"authors":{"en":[{"name":"Segawa Hiroko"},{"name":"Kaneko Ichiro"},{"name":"Yamanaka Setsuko"},{"name":"Ito Mikiko"},{"name":"Kuwahata Masashi"},{"name":"Inoue Yoshio"},{"name":"Kato Shigeaki"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"瀬川 博子"},{"name":"金子 一郎"},{"name":"山中 説子"},{"name":"伊藤 美紀子"},{"name":"桑波田 雅士"},{"name":"井上 善雄"},{"name":"加藤 茂明"},{"name":"宮本 賢一"}]},"description":{"en":"Recent studies suggest that vitamin D may play a role in intestinal Na(+)-dependent phosphate transport adaptation to variable levels of dietary P(i). Therefore, the goal of the current study was to assess Na(+)-dependent P(i) cotransport activity in transgenic mice to determine whether vitamin D is an essential mediator of this process. Intestinal brush-border membrane (BBM), Na(+)-dependent P(i) cotransport activity was significantly decreased in vitamin D receptor (VDR) null [VDR (-/-)] mice compared with wild-type (VDR+/+) mice. While intestinal Na-P(i) cotransporter (type IIb) mRNA levels were similar in VDR (-/-) and VDR (+/+) mice, type IIb Na-P(i) cotransporter protein expression was markedly suppressed in VDR (-/-) mice compared with VDR (+/+) mice. Furthermore, Na-P(i) cotransport activity in renal BBM was similar in VDR (-/-) and VDR (+/+) mice, but type IIa Na-P(i) cotransporter protein expression was decreased in VDR (-/-) mice. After administration of a low-P(i) diet, type IIb protein expression was significantly increased in VDR (+/+) and VDR (-/-) mice, and type IIb protein expression was present in the intestinal BBM of VDR (-/-) mice. These data demonstrate that intestinal Na-P(i) cotransport adaptation to a low-P(i) diet occurs independently of vitamin D.","ja":"Recent studies suggest that vitamin D may play a role in intestinal Na(+)-dependent phosphate transport adaptation to variable levels of dietary P(i). Therefore, the goal of the current study was to assess Na(+)-dependent P(i) cotransport activity in transgenic mice to determine whether vitamin D is an essential mediator of this process. Intestinal brush-border membrane (BBM), Na(+)-dependent P(i) cotransport activity was significantly decreased in vitamin D receptor (VDR) null [VDR (-/-)] mice compared with wild-type (VDR+/+) mice. While intestinal Na-P(i) cotransporter (type IIb) mRNA levels were similar in VDR (-/-) and VDR (+/+) mice, type IIb Na-P(i) cotransporter protein expression was markedly suppressed in VDR (-/-) mice compared with VDR (+/+) mice. Furthermore, Na-P(i) cotransport activity in renal BBM was similar in VDR (-/-) and VDR (+/+) mice, but type IIa Na-P(i) cotransporter protein expression was decreased in VDR (-/-) mice. After administration of a low-P(i) diet, type IIb protein expression was significantly increased in VDR (+/+) and VDR (-/-) mice, and type IIb protein expression was present in the intestinal BBM of VDR (-/-) mice. These data demonstrate that intestinal Na-P(i) cotransport adaptation to a low-P(i) diet occurs independently of vitamin D."},"publication_date":"2004-03-02","publication_name":{"en":"American Journal of Physiology, Renal Physiology","ja":"American Journal of Physiology, Renal Physiology"},"volume":"Vol.287","number":"No.1","starting_page":"F39","ending_page":"F47","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1152/ajprenal.00375.2003"],"issn":["1931-857X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/14558883","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=90087","label":"url"}],"paper_title":{"en":"Interaction of a farnesylated protein with rwnal type a Na/Pi co-transporter in response to parathyroid hormone and dietary phosphate.","ja":"Interaction of a farnesylated protein with rwnal type a Na/Pi co-transporter in response to parathyroid hormone and dietary phosphate."},"authors":{"en":[{"name":"Ito Mikiko"},{"name":"Iidawa Sachi"},{"name":"Izuka Michiyo"},{"name":"Haito Sakiko"},{"name":"Segawa Hiroko"},{"name":"Kuwahata Masashi"},{"name":"Ohkido Ichiro"},{"name":"Ohno Hiroshi"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"伊藤 美紀子"},{"name":"飯田和 祥"},{"name":"猪塚 倫代"},{"name":"拝藤 紗貴子"},{"name":"瀬川 博子"},{"name":"桑波田 雅士"},{"name":"大城戸 一郎"},{"name":"大野 博"},{"name":"宮本 賢一"}]},"description":{"en":"Treatment with PTH (parathyroid hormone) or a high-P(i) diet causes internalization of the type IIa sodium-dependent phosphate (Na/P(i) IIa) co-transporter from the apical membrane and its degradation in the lysosome. A dibasic amino acid motif (KR) in the third intracellular loop of the co-transporter is essential for protein's PTH-induced retrieval. To elucidate the mechanism of internalization of Na/P(i) IIa, we identified the interacting protein for the endocytic motif by yeast two-hybrid screening. We found a strong interaction of the Na/P(i) IIa co-transporter with a small protein known as the PEX19 (human peroxisomal farnesylated protein; PxF, Pex19p). PEX19 can bind to the KR motif, but not to a mutant with this motif replaced with NI residues. PEX19 is highly expressed in mouse and rat kidney. Western blot analysis indicates that PEX19 is located in the cytosolic and brush-border membrane fractions (microvilli and the subapical component). Overexpression of PEX19 stimulated the endocytosis of the Na/P(i) IIa co-transporter in opossum kidney cells in the absence of PTH. In conclusion, the present study indicates that PEX19 may be actively involved in controlling the internalization and trafficking of the Na/P(i) IIa co-transporter.","ja":"Treatment with PTH (parathyroid hormone) or a high-P(i) diet causes internalization of the type IIa sodium-dependent phosphate (Na/P(i) IIa) co-transporter from the apical membrane and its degradation in the lysosome. A dibasic amino acid motif (KR) in the third intracellular loop of the co-transporter is essential for protein's PTH-induced retrieval. To elucidate the mechanism of internalization of Na/P(i) IIa, we identified the interacting protein for the endocytic motif by yeast two-hybrid screening. We found a strong interaction of the Na/P(i) IIa co-transporter with a small protein known as the PEX19 (human peroxisomal farnesylated protein; PxF, Pex19p). PEX19 can bind to the KR motif, but not to a mutant with this motif replaced with NI residues. PEX19 is highly expressed in mouse and rat kidney. Western blot analysis indicates that PEX19 is located in the cytosolic and brush-border membrane fractions (microvilli and the subapical component). Overexpression of PEX19 stimulated the endocytosis of the Na/P(i) IIa co-transporter in opossum kidney cells in the absence of PTH. In conclusion, the present study indicates that PEX19 may be actively involved in controlling the internalization and trafficking of the Na/P(i) IIa co-transporter."},"publication_date":"2004-02-01","publication_name":{"en":"The Biochemical Journal","ja":"The Biochemical Journal"},"volume":"Vol.377","number":"No.3","starting_page":"607","ending_page":"616","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1042/BJ20031223"],"issn":["1470-8728"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/14691680","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1573950399836536704/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=90102","label":"url"}],"paper_title":{"en":"Cloning and characterization of three PHEX homologues in Drosophila.","ja":"Cloning and characterization of three PHEX homologues in Drosophila."},"authors":{"en":[{"name":"Ito Mikiko"},{"name":"Sachi Iidawa"},{"name":"Michiyo Izuka"},{"name":"Sakiko Haito"},{"name":"Segawa Hiroko"},{"name":"Kuwahata Masashi"},{"name":"Ichiro Ohkido"},{"name":"Hiroshi Ohno"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"伊藤 美紀子"},{"name":"飯田和 祥"},{"name":"猪塚 倫代"},{"name":"拝藤 紗貴子"},{"name":"瀬川 博子"},{"name":"桑波田 雅士"},{"name":"大城戸 一郎"},{"name":"大野 博"},{"name":"宮本 賢一"}]},"description":{"en":"Inactivating mutations and/or deletions of PHEX ( Phosphate-regulating gene with Homologies to Endopeptidase on the X chromosome) are responsible for X-linked hypophosphatemic rickets in humans. In the present study, three Drosophila PHEX homologues (dPHEX-1, -2, -3) were isolated by the screening of a Drosophila cDNA library and expressed sequence tag (EST) database. The structural region involving motif II: (456)WMXXXTKXXAXXK(468) (numbered according to human PHEX), motif VI: (602)WW(603), and motif VIII: (746)CXLW(749) was conserved in the dPHEX family. Zinc-coordinating motifs (HEFTH and GENIADNGG) were also conserved in the dPHEX family. All three dPHEX genes were expressed during all stages of Drosophila development. The expression of dPHEX-1 was suppressed by dietary phosphate deprivation, but the expression of dPHEX-2 and that of dPHEX-3 were not affected. In-situ hybridization showed a ubiquitous distribution of dPHEX-1 and dPHEX-2, while dPHEX-3 was highly expressed in the larval brain. In an analysis of subcellular localization, dPHEX-1 was localized to intracellular organelles and dPHEX-3 was localized predominately in the plasma membrane of Drosophila embryonic S2 cells. Homozygosity of a dPHEX-1 mutation, a transposon insertion in the dPHEX-1 promoter region, was completely lethal at an early stage of embryonic development. The present study indicates that three homologues are likely involved in the phosphate homeostasis of Drosophila.","ja":"Inactivating mutations and/or deletions of PHEX ( Phosphate-regulating gene with Homologies to Endopeptidase on the X chromosome) are responsible for X-linked hypophosphatemic rickets in humans. In the present study, three Drosophila PHEX homologues (dPHEX-1, -2, -3) were isolated by the screening of a Drosophila cDNA library and expressed sequence tag (EST) database. The structural region involving motif II: (456)WMXXXTKXXAXXK(468) (numbered according to human PHEX), motif VI: (602)WW(603), and motif VIII: (746)CXLW(749) was conserved in the dPHEX family. Zinc-coordinating motifs (HEFTH and GENIADNGG) were also conserved in the dPHEX family. All three dPHEX genes were expressed during all stages of Drosophila development. The expression of dPHEX-1 was suppressed by dietary phosphate deprivation, but the expression of dPHEX-2 and that of dPHEX-3 were not affected. In-situ hybridization showed a ubiquitous distribution of dPHEX-1 and dPHEX-2, while dPHEX-3 was highly expressed in the larval brain. In an analysis of subcellular localization, dPHEX-1 was localized to intracellular organelles and dPHEX-3 was localized predominately in the plasma membrane of Drosophila embryonic S2 cells. Homozygosity of a dPHEX-1 mutation, a transposon insertion in the dPHEX-1 promoter region, was completely lethal at an early stage of embryonic development. The present study indicates that three homologues are likely involved in the phosphate homeostasis of Drosophila."},"publication_date":"2004-02","publication_name":{"en":"Journal of Bone and Mineral Metabolism","ja":"Journal of Bone and Mineral Metabolism"},"volume":"Vol.22","number":"No.1","starting_page":"3","ending_page":"11","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00774-003-0440-8"],"issn":["0914-8779"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12939463","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=147270","label":"url"}],"paper_title":{"en":"Combination Treatment with 1α,25-Dihydroxyvitamin D3 and 9-cis-Retinoic Acid Directly Inhibits Human Telomerase Reverse Transcriptase Transcription in Prostate Cancer Cells","ja":"Combination Treatment with 1α,25-Dihydroxyvitamin D3 and 9-cis-Retinoic Acid Directly Inhibits Human Telomerase Reverse Transcriptase Transcription in Prostate Cancer Cells"},"authors":{"en":[{"name":"Ikeda Naoya"},{"name":"Uemura Hiroji"},{"name":"Ishiguro Hitoshi"},{"name":"Hori Mayumi"},{"name":"Hosaka Masahiko"},{"name":"Kyo Satoru"},{"name":"Miyamoto Ken-ichi"},{"name":"Takeda Eiji"},{"name":"Kubota Yoshinobu"}],"ja":[{"name":"Ikeda Naoya"},{"name":"Uemura Hiroji"},{"name":"Ishiguro Hitoshi"},{"name":"Hori Mayumi"},{"name":"Hosaka Masahiko"},{"name":"Kyo Satoru"},{"name":"宮本 賢一"},{"name":"武田 英二"},{"name":"Kubota Yoshinobu"}]},"description":{"en":"The vitamin D(3) receptor, which is the nuclear receptor for 1alpha,25-dihydroxyvitamin D(3) (VD(3)), forms a heterodimer with the retinoid X receptor (RXR), which is the nuclear receptor for 9-cis-retinoic acid (9-cis-RA). The heterodimer binds to a specific response element consisting of two directly repeated pairs of motifs, AGGTGA, spaced by three nucleotides [direct repeat (DR) 3] and modulates the expression of VD(3)-responsive genes. Telomerase activity, which is seen in most immortal cells and germ cells, is a complex of enzymes that maintain the length of telomeres. One of the major components of human telomerase, human telomerase reverse transcriptase (hTERT), is the catalytic subunit, and the expression of hTERT might correlate most strongly with telomerase activity. We found that the sequence of 5'-AGTTCATGGAGTTCA-3' (DR3') is similar to that of DR3 in the promoter region of hTERT. Our results showed that the combination of VD(3) and 9-cis-RA inhibited telomerase activity through direct interaction of the heterodimer of vitamin D(3) receptor and RXR with the DR3' sequence in the hTERT promoter as well as the combination of VD(3) and selective RXR ligand did. Also, in vivo data showed that the growth of xenografts in nude mice was inhibited by VD(3) and 9-cis-RA. The results of the present study provide evidence on the molecular mechanism of the inhibition of cell growth by these agents, and they could be novel therapeutic agents for prostate cancer.","ja":"The vitamin D(3) receptor, which is the nuclear receptor for 1alpha,25-dihydroxyvitamin D(3) (VD(3)), forms a heterodimer with the retinoid X receptor (RXR), which is the nuclear receptor for 9-cis-retinoic acid (9-cis-RA). The heterodimer binds to a specific response element consisting of two directly repeated pairs of motifs, AGGTGA, spaced by three nucleotides [direct repeat (DR) 3] and modulates the expression of VD(3)-responsive genes. Telomerase activity, which is seen in most immortal cells and germ cells, is a complex of enzymes that maintain the length of telomeres. One of the major components of human telomerase, human telomerase reverse transcriptase (hTERT), is the catalytic subunit, and the expression of hTERT might correlate most strongly with telomerase activity. We found that the sequence of 5'-AGTTCATGGAGTTCA-3' (DR3') is similar to that of DR3 in the promoter region of hTERT. Our results showed that the combination of VD(3) and 9-cis-RA inhibited telomerase activity through direct interaction of the heterodimer of vitamin D(3) receptor and RXR with the DR3' sequence in the hTERT promoter as well as the combination of VD(3) and selective RXR ligand did. Also, in vivo data showed that the growth of xenografts in nude mice was inhibited by VD(3) and 9-cis-RA. The results of the present study provide evidence on the molecular mechanism of the inhibition of cell growth by these agents, and they could be novel therapeutic agents for prostate cancer."},"publication_date":"2003-08","publication_name":{"en":"Molecular Cancer Therapeutics","ja":"Molecular Cancer Therapeutics"},"volume":"Vol.2","number":"No.8","starting_page":"739","ending_page":"746","languages":["eng"],"referee":true,"identifiers":{"issn":["1535-7163"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://www.springerlink.com/content/8t7dbaktcwm059eu/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12851820","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=90045","label":"url"}],"paper_title":{"en":"Effect of hydrolysis-resistant FGF23-R179Q on dietary phosphate regulation of the renal type-II Na/Pi transporter.","ja":"Effect of hydrolysis-resistant FGF23-R179Q on dietary phosphate regulation of the renal type-II Na/Pi transporter."},"authors":{"en":[{"name":"Segawa Hiroko"},{"name":"Kawakami Eri"},{"name":"Kaneko Ichiro"},{"name":"Kuwahata Masashi"},{"name":"Ito Mikiko"},{"name":"Kusano Kenichiro"},{"name":"Saito Hitoshi"},{"name":"Fukushima Naoshi"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"瀬川 博子"},{"name":"川上 絵里"},{"name":"金子 一郎"},{"name":"桑波田 雅士"},{"name":"伊藤 美紀子"},{"name":"草野 健一郎"},{"name":"斉藤 仁"},{"name":"福島 直"},{"name":"宮本 賢一"}]},"description":{"en":"Fibroblast growth factor 23 (FGF23), a phosphaturic factor, is involved in the regulation of renal inorganic phosphate (Pi) reabsorption. Proteolysis-resistant FGF23 mutants expressed in rodents reduce Pi uptake in both intestine and kidney, independent of parathyroid hormone action. In the present study, we investigated whether FGF23 affects dietary regulation of Na(+)-dependent Pi (Na/Pi) cotransport in the rat kidney using wild-type FGF23 and an R179Q mutant, which disrupts a consensus proteolytic cleavage motif. Rats injected with naked human FGF23 DNA (wild-type or R179Q mutant) expressed the human FGF23 transcript in the liver. In those animals, plasma calcium and parathyroid hormone levels were not affected by FGF23 (either wild-type or R179Q mutant). FGF23-R179Q did, however, significantly decrease plasma Pi and renal Na/Pi cotransport activity and also the level of type-IIc Na/Pi cotransporter protein in brush-border membrane vesicles (BBMVs) from normal rat kidney. Western blot and immunohistochemical analyses in rats fed a low-Pi diet showed the levels of types-IIa and -IIc Na/Pi cotransporters to be markedly increased. After injection of FGF23-R179Q DNA into the rats fed a low-Pi diet, the levels of the types-IIa and -IIc transporter proteins were decreased. The FGF23 mutant thus blunts the signalling of Pi deprivation to the renal type-II Na/Pi cotransporter, suggesting that the FGF23 pathway could be involved in the signalling of dietary Pi.","ja":"Fibroblast growth factor 23 (FGF23), a phosphaturic factor, is involved in the regulation of renal inorganic phosphate (Pi) reabsorption. Proteolysis-resistant FGF23 mutants expressed in rodents reduce Pi uptake in both intestine and kidney, independent of parathyroid hormone action. In the present study, we investigated whether FGF23 affects dietary regulation of Na(+)-dependent Pi (Na/Pi) cotransport in the rat kidney using wild-type FGF23 and an R179Q mutant, which disrupts a consensus proteolytic cleavage motif. Rats injected with naked human FGF23 DNA (wild-type or R179Q mutant) expressed the human FGF23 transcript in the liver. In those animals, plasma calcium and parathyroid hormone levels were not affected by FGF23 (either wild-type or R179Q mutant). FGF23-R179Q did, however, significantly decrease plasma Pi and renal Na/Pi cotransport activity and also the level of type-IIc Na/Pi cotransporter protein in brush-border membrane vesicles (BBMVs) from normal rat kidney. Western blot and immunohistochemical analyses in rats fed a low-Pi diet showed the levels of types-IIa and -IIc Na/Pi cotransporters to be markedly increased. After injection of FGF23-R179Q DNA into the rats fed a low-Pi diet, the levels of the types-IIa and -IIc transporter proteins were decreased. The FGF23 mutant thus blunts the signalling of Pi deprivation to the renal type-II Na/Pi cotransporter, suggesting that the FGF23 pathway could be involved in the signalling of dietary Pi."},"publication_date":"2003-07-08","publication_name":{"en":"Pflügers Archiv : European Journal of Physiology","ja":"Pflügers Archiv : European Journal of Physiology"},"volume":"Vol.446","number":"No.5","starting_page":"585","ending_page":"592","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s00424-003-1084-1"],"issn":["0031-6768"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12745071","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92028","label":"url"}],"paper_title":{"en":"Increase in IP3 and intracellular Ca2+ induced by phosphate depletion in LLC-PK1 cells.","ja":"Increase in IP3 and intracellular Ca2+ induced by phosphate depletion in LLC-PK1 cells."},"authors":{"en":[{"name":"Taketani Yutaka"},{"name":"Nomoto Mayumi"},{"name":"Yamamoto Hironori"},{"name":"Isshiki Masashi"},{"name":"Morita Kyoko"},{"name":"Arai Hidekazu"},{"name":"Miyamoto Ken-ichi"},{"name":"Kato Shigeaki"},{"name":"Takeda Eiji"}],"ja":[{"name":"竹谷 豊"},{"name":"野本 真由美"},{"name":"山本 浩範"},{"name":"一色 政志"},{"name":"森田 恭子"},{"name":"新井 英一"},{"name":"宮本 賢一"},{"name":"加藤 茂明"},{"name":"武田 英二"}]},"description":{"en":"The mechanisms by which Pi depletion rapidly regulates gene expression and cellular function have not been clarified. Here, we found a rapid increase in intracellular ionized calcium [Ca(2+)](i) by phosphate depletion in LLC-PK(1) cells using confocal microscopy with the green-fluorescence protein based calcium indicator \"yellow cameleon 2.1.\" The increase of [Ca(2+)](i) was observed in the presence or absence of extracellular Ca(2+). At the same time, an approximately twofold increase in intracellular inositol 1,4,5-triphosphate (IP(3)) occurred in response to the acute Pi depletion in the medium. Furthermore, 2-aminoethoxydiphenyl borate completely blocked the [Ca(2+)](i) increase induced by Pi depletion. These results suggest that Pi depletion causes IP(3)-mediated release of Ca(2+) from intracellular Ca(2+) pools and rapidly increases [Ca(2+)](i) in LLC-PK(1) cells.","ja":"The mechanisms by which Pi depletion rapidly regulates gene expression and cellular function have not been clarified. Here, we found a rapid increase in intracellular ionized calcium [Ca(2+)](i) by phosphate depletion in LLC-PK(1) cells using confocal microscopy with the green-fluorescence protein based calcium indicator \"yellow cameleon 2.1.\" The increase of [Ca(2+)](i) was observed in the presence or absence of extracellular Ca(2+). At the same time, an approximately twofold increase in intracellular inositol 1,4,5-triphosphate (IP(3)) occurred in response to the acute Pi depletion in the medium. Furthermore, 2-aminoethoxydiphenyl borate completely blocked the [Ca(2+)](i) increase induced by Pi depletion. These results suggest that Pi depletion causes IP(3)-mediated release of Ca(2+) from intracellular Ca(2+) pools and rapidly increases [Ca(2+)](i) in LLC-PK(1) cells."},"publication_date":"2003-05-30","publication_name":{"en":"Biochemical and Biophysical Research Communications","ja":"Biochemical and Biophysical Research Communications"},"volume":"Vol.305","number":"No.2","starting_page":"287","ending_page":"291","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0006-291X(03)00750-2"],"issn":["0006-291X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=89533","label":"url"}],"paper_title":{"en":"肝障害モデルラットへのBCAA高含有製剤投与による低アルブミン血症改善機構の検討","ja":"肝障害モデルラットへのBCAA高含有製剤投与による低アルブミン血症改善機構の検討"},"authors":{"en":[{"name":"Kuwahata Masashi"},{"name":"Segawa Hiroko"},{"name":"Ito Mikiko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"桑波田 雅士"},{"name":"瀬川 博子"},{"name":"伊藤 美紀子"},{"name":"宮本 賢一"}]},"publication_date":"2002-07","publication_name":{"en":"日本病態栄養学会誌","ja":"日本病態栄養学会誌"},"volume":"Vol.5","number":"No.1","starting_page":"21","ending_page":"25","referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/80015405488/","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11880379","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1572824501584477568/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=88890","label":"url"}],"paper_title":{"en":"Growth-related renal Type II Na/Pi cotransporter.","ja":"Growth-related renal Type II Na/Pi cotransporter."},"authors":{"en":[{"name":"Segawa Hiroko"},{"name":"Kaneko Ichiro"},{"name":"Takahashi Akira"},{"name":"Kuwahata Masashi"},{"name":"Ito Mikiko"},{"name":"Ichiro Ohkido"},{"name":"Tatsumi Sawako"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"瀬川 博子"},{"name":"金子 一郎"},{"name":"髙橋 章"},{"name":"桑波田 雅士"},{"name":"伊藤 美紀子"},{"name":"大城戸 一郎"},{"name":"辰巳 佐和子"},{"name":"宮本 賢一"}]},"publication_date":"2002-05","publication_name":{"en":"The Journal of Biological Chemistry","ja":"The Journal of Biological Chemistry"},"volume":"Vol.277","number":"No.22","starting_page":"19665","ending_page":"19672","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1074/jbc.M200943200"],"issn":["0021-9258"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/12171429","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=147065","label":"url"}],"paper_title":{"en":"Phosphorus supply per capita from food in Japan between 1960 and 1995","ja":"Phosphorus supply per capita from food in Japan between 1960 and 1995"},"authors":{"en":[{"name":"Takeda Eiji"},{"name":"Sakamoto Kyoko"},{"name":"Yokota Kimi"},{"name":"Shinohara Maiko"},{"name":"Taketani Yutaka"},{"name":"Morita Kyoko"},{"name":"Yamamoto Hironori"},{"name":"Miyamoto Ken-ichi"},{"name":"Shibayama Mitsuo"}],"ja":[{"name":"武田 英二"},{"name":"Sakamoto Kyoko"},{"name":"Yokota Kimi"},{"name":"Shinohara Maiko"},{"name":"竹谷 豊"},{"name":"森田 恭子"},{"name":"山本 浩範"},{"name":"宮本 賢一"},{"name":"Shibayama Mitsuo"}]},"description":{"en":"The awareness of phosphorus intake is important because hyperphosphatemia and hypophosphatemia both impair bone metabolism. Phosphorus consumption from food was obtained from values in the Food Balance Sheet (PBS) of Japan from 1960 to 1995. The amounts of phosphorus calculated from the FBS increased gradually from 1,243 mg/d in 1960 to 1,332 mg/d in 1975 and to 1,421 mg/d in 1995. This is explained by the increased consumption of cow's milk and milk products, meat, and chicken eggs. The main foods supplying phosphorus in 1995 were cereals, milk and milk products, fishes and shellfishes, and vegetables; their contributions were 24.4, 15.8, 14.2, and 10.9%, respectively. The phosphorus-to-calcium ratio calculated from the FBS was 3.51 in 1960, which decreased to 2.89 in 1975 and 2.44 in 1995. Therefore total phosphorus consumption in 1995 was presumably more than 1,500 mg/d when imported food containing phosphorus and the consumption of phosphorus-containing food additives in Japan are also considered. These findings suggest that the phosphorus consumption estimated from the FBS is increasing and that more attention should be paid to the maintenance of healthy bones in Japan, where the average amount of calcium intake is less than 600 mg/d.","ja":"The awareness of phosphorus intake is important because hyperphosphatemia and hypophosphatemia both impair bone metabolism. Phosphorus consumption from food was obtained from values in the Food Balance Sheet (PBS) of Japan from 1960 to 1995. The amounts of phosphorus calculated from the FBS increased gradually from 1,243 mg/d in 1960 to 1,332 mg/d in 1975 and to 1,421 mg/d in 1995. This is explained by the increased consumption of cow's milk and milk products, meat, and chicken eggs. The main foods supplying phosphorus in 1995 were cereals, milk and milk products, fishes and shellfishes, and vegetables; their contributions were 24.4, 15.8, 14.2, and 10.9%, respectively. The phosphorus-to-calcium ratio calculated from the FBS was 3.51 in 1960, which decreased to 2.89 in 1975 and 2.44 in 1995. Therefore total phosphorus consumption in 1995 was presumably more than 1,500 mg/d when imported food containing phosphorus and the consumption of phosphorus-containing food additives in Japan are also considered. These findings suggest that the phosphorus consumption estimated from the FBS is increasing and that more attention should be paid to the maintenance of healthy bones in Japan, where the average amount of calcium intake is less than 600 mg/d."},"publication_date":"2002-04","publication_name":{"en":"Journal of Nutritional Science and Vitaminology","ja":"Journal of Nutritional Science and Vitaminology"},"volume":"Vol.48","number":"No.2","starting_page":"102","ending_page":"108","languages":["eng"],"referee":true,"identifiers":{"issn":["0301-4800"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=130551","label":"url"}],"paper_title":{"en":"肝障害モデルラットへのBCAA高含有製剤投与による低アルブミン血症改善機構の検討","ja":"肝障害モデルラットへのBCAA高含有製剤投与による低アルブミン血症改善機構の検討"},"authors":{"en":[{"name":"Kuwahata Masashi"},{"name":"Segawa Hiroko"},{"name":"Ito Mikiko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"桑波田 雅士"},{"name":"瀬川 博子"},{"name":"伊藤 美紀子"},{"name":"宮本 賢一"}]},"publication_date":"2002","publication_name":{"en":"日本病態栄養学会誌","ja":"日本病態栄養学会誌"},"volume":"Vol.5","number":"No.1","starting_page":"21","ending_page":"25","languages":["jpn"],"referee":true,"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11557028","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146720","label":"url"}],"paper_title":{"en":"Human L-type amino acid transporter 1(LAT1):/characterization of function and expression in tumor cell lines","ja":"Human L-type amino acid transporter 1(LAT1):/characterization of function and expression in tumor cell lines"},"authors":{"en":[{"name":"Yanagida Osamu"},{"name":"Kanai Yoshikatsu"},{"name":"Chairoungdua Arthit"},{"name":"Kim Kyung Do"},{"name":"Segawa Hiroko"},{"name":"Nii Tomoko"},{"name":"Cha Ho Seok"},{"name":"Matsuo Hirotaka"},{"name":"Fukushima Jun-ichi"},{"name":"Fukasawa Yoshiki"},{"name":"Tani Yoshiko"},{"name":"Taketani Yutaka"},{"name":"Uchino Hiroshi"},{"name":"Kim Young Ju"},{"name":"Inatomi Jun"},{"name":"Okayasu Isao"},{"name":"Miyamoto Ken-ichi"},{"name":"Takeda Eiji"},{"name":"Goya Tomoyuki"},{"name":"Endou Hitoshi"}],"ja":[{"name":"Yanagida Osamu"},{"name":"Kanai Yoshikatsu"},{"name":"Chairoungdua Arthit"},{"name":"Kim Kyung Do"},{"name":"瀬川 博子"},{"name":"Nii Tomoko"},{"name":"Cha Ho Seok"},{"name":"Matsuo Hirotaka"},{"name":"Fukushima Jun-ichi"},{"name":"Fukasawa Yoshiki"},{"name":"Tani Yoshiko"},{"name":"竹谷 豊"},{"name":"Uchino Hiroshi"},{"name":"Kim Young Ju"},{"name":"Inatomi Jun"},{"name":"Okayasu Isao"},{"name":"宮本 賢一"},{"name":"武田 英二"},{"name":"Goya Tomoyuki"},{"name":"Endou Hitoshi"}]},"description":{"en":"System L is a major nutrient transport system responsible for the transport of large neutral amino acids including several essential amino acids. We previously identified a transporter (L-type amino acid transporter 1: LAT1) subserving system L in C6 rat glioma cells and demonstrated that LAT1 requires 4F2 heavy chain (4F2hc) for its functional expression. Since its oncofetal expression was suggested in the rat liver, it has been proposed that LAT1 plays a critical role in cell growth and proliferation. In the present study, we have examined the function of human LAT1 (hLAT1) and its expression in human tissues and tumor cell lines. When expressed in Xenopus oocytes with human 4F2hc (h4F2hc), hLAT1 transports large neutral amino acids with high affinity (K(m)= approximately 15- approximately 50 microM) and L-glutamine and L-asparagine with low affinity (K(m)= approximately 1.5- approximately 2 mM). hLAT1 also transports D-amino acids such as D-leucine and D-phenylalanine. In addition, we show that hLAT1 accepts an amino acid-related anti-cancer agent melphalan. When loaded intracellularly, L-leucine and L-glutamine but not L-alanine are effluxed by extracellular substrates, confirming that hLAT1 mediates an amino acid exchange. hLAT1 mRNA is highly expressed in the human fetal liver, bone marrow, placenta, testis and brain. We have found that, while all the tumor cell lines examined express hLAT1 messages, the expression of h4F2hc is varied particularly in leukemia cell lines. In Western blot analysis, hLAT1 and h4F2hc have been confirmed to be linked to each other via a disulfide bond in T24 human bladder carcinoma cells. Finally, in in vitro translation, we show that hLAT1 is not a glycosylated protein even though an N-glycosylation site has been predicted in its extracellular loop, consistent with the property of the classical 4F2 light chain. The properties of the hLAT1/h4F2hc complex would support the roles of this transporter in providing cells with essential amino acids for cell growth and cellular responses, and in distributing amino acid-related compounds.","ja":"System L is a major nutrient transport system responsible for the transport of large neutral amino acids including several essential amino acids. We previously identified a transporter (L-type amino acid transporter 1: LAT1) subserving system L in C6 rat glioma cells and demonstrated that LAT1 requires 4F2 heavy chain (4F2hc) for its functional expression. Since its oncofetal expression was suggested in the rat liver, it has been proposed that LAT1 plays a critical role in cell growth and proliferation. In the present study, we have examined the function of human LAT1 (hLAT1) and its expression in human tissues and tumor cell lines. When expressed in Xenopus oocytes with human 4F2hc (h4F2hc), hLAT1 transports large neutral amino acids with high affinity (K(m)= approximately 15- approximately 50 microM) and L-glutamine and L-asparagine with low affinity (K(m)= approximately 1.5- approximately 2 mM). hLAT1 also transports D-amino acids such as D-leucine and D-phenylalanine. In addition, we show that hLAT1 accepts an amino acid-related anti-cancer agent melphalan. When loaded intracellularly, L-leucine and L-glutamine but not L-alanine are effluxed by extracellular substrates, confirming that hLAT1 mediates an amino acid exchange. hLAT1 mRNA is highly expressed in the human fetal liver, bone marrow, placenta, testis and brain. We have found that, while all the tumor cell lines examined express hLAT1 messages, the expression of h4F2hc is varied particularly in leukemia cell lines. In Western blot analysis, hLAT1 and h4F2hc have been confirmed to be linked to each other via a disulfide bond in T24 human bladder carcinoma cells. Finally, in in vitro translation, we show that hLAT1 is not a glycosylated protein even though an N-glycosylation site has been predicted in its extracellular loop, consistent with the property of the classical 4F2 light chain. The properties of the hLAT1/h4F2hc complex would support the roles of this transporter in providing cells with essential amino acids for cell growth and cellular responses, and in distributing amino acid-related compounds."},"publication_date":"2001-10-01","publication_name":{"en":"Biochimica et Biophysica Acta (BBA) - Biomembranes","ja":"Biochimica et Biophysica Acta (BBA) - Biomembranes"},"volume":"Vol.1514","number":"No.2","starting_page":"291","ending_page":"302","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0005-2736(01)00384-4"],"issn":["0005-2736"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=130554","label":"url"}],"paper_title":{"en":") Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation","ja":") Molecular events involved in up-regulating human Na+-independent neutral amino acid transporter LAT1 during T-cell activation"},"authors":{"en":[{"name":"Nii Tomoko"},{"name":"Segawa Hiroko"},{"name":"Taketani Yutaka"},{"name":"Tani Yoshiko"},{"name":"Ohkido Makiko"},{"name":"Kishida Sachie"},{"name":"Ito Mikiko"},{"name":"Endou Hitoshi"},{"name":"Kanai Yoshikatsu"},{"name":"Takeda Eiji"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Nii Tomoko"},{"name":"瀬川 博子"},{"name":"竹谷 豊"},{"name":"Tani Yoshiko"},{"name":"Ohkido Makiko"},{"name":"Kishida Sachie"},{"name":"伊藤 美紀子"},{"name":"Endou Hitoshi"},{"name":"Kanai Yoshikatsu"},{"name":"武田 英二"},{"name":"宮本 賢一"}]},"publication_date":"2001-09-15","publication_name":{"en":"The Biochemical Journal","ja":"The Biochemical Journal"},"volume":"Vol.358","number":"No.3","starting_page":"693","ending_page":"704","languages":["eng"],"referee":true,"identifiers":{"issn":["0264-6021"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/11498730","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146719","label":"url"}],"paper_title":{"en":"Hypophosphatemic rickets accompanying McCune Albright syndrome: evidence that a humoral factor causes hypophosphatemia","ja":"Hypophosphatemic rickets accompanying McCune Albright syndrome: evidence that a humoral factor causes hypophosphatemia"},"authors":{"en":[{"name":"Yamamoto Takehisa"},{"name":"Miyamoto Ken-ichi"},{"name":"Ozono Keiichi"},{"name":"Taketani Yutaka"},{"name":"Katai Kanako"},{"name":"Miyauchi Akimitsu"},{"name":"Shima Masaaki"},{"name":"Yoshikawa Hideki"},{"name":"Yoh Kosei"},{"name":"Takeda Eiji"},{"name":"Okada Shintaro"}],"ja":[{"name":"Yamamoto Takehisa"},{"name":"宮本 賢一"},{"name":"Ozono Keiichi"},{"name":"竹谷 豊"},{"name":"Katai Kanako"},{"name":"Miyauchi Akimitsu"},{"name":"Shima Masaaki"},{"name":"Yoshikawa Hideki"},{"name":"Yoh Kosei"},{"name":"武田 英二"},{"name":"Okada Shintaro"}]},"description":{"en":"McCune-Albright syndrome (MAS) is sometimes complicated by hypophosphatemia. However, it remains unclear whether a humoral factor is associated with the cause of hypophosphatemia. We isolated cells with mutations of the Gsalpha gene from fibrous bone dysplasia tissues of two MAS patients (MAS cells). Severe combined immunodeficiency (SCID) mice were subjected to experiments using from one of these cells patients. Effects of conditioned media (CM) isolated from MAS cells (MAS-CM) on phosphate transport were investigated by using rat renal slices, the renal cell line OK-B, rat intestinal rings and the human intestinal cell line Caco-2. In addition, the effects of MAS-CM on human sodium-dependent phosphate transporter (NPT2) gene promoter activity expression were investigated in the renal cell line OK-B2400 and were compared with the effects of CM isolated from a patient with oncogenic hypophosphatemic osteomalacia (OHO). MAS cells caused significant hypophosphatemia (P < 0.05) and elevated serum alkaline phosphatase activity (P < 0.05) in SCID mice. The MAS-CM significantly inhibited phosphate uptake in everted intestinal rings (P < 0.01), whereas it had no effect on glucose uptake. The MAS-CM had no effect on either phosphate uptake in the kidney or NPT2 gene promoter activity. In contrast, the CM of the OHO patient significantly inhibited phosphate uptake and NPT2 gene promoter activity. These results indicate that the humoral factor derived from fibrous dysplasia cells of the MAS patient is different to that from OHO patients, because the humoral factor from the MAS patient inhibited phosphate transport not in the kidney but in the intestine.","ja":"McCune-Albright syndrome (MAS) is sometimes complicated by hypophosphatemia. However, it remains unclear whether a humoral factor is associated with the cause of hypophosphatemia. We isolated cells with mutations of the Gsalpha gene from fibrous bone dysplasia tissues of two MAS patients (MAS cells). Severe combined immunodeficiency (SCID) mice were subjected to experiments using from one of these cells patients. Effects of conditioned media (CM) isolated from MAS cells (MAS-CM) on phosphate transport were investigated by using rat renal slices, the renal cell line OK-B, rat intestinal rings and the human intestinal cell line Caco-2. In addition, the effects of MAS-CM on human sodium-dependent phosphate transporter (NPT2) gene promoter activity expression were investigated in the renal cell line OK-B2400 and were compared with the effects of CM isolated from a patient with oncogenic hypophosphatemic osteomalacia (OHO). MAS cells caused significant hypophosphatemia (P < 0.05) and elevated serum alkaline phosphatase activity (P < 0.05) in SCID mice. The MAS-CM significantly inhibited phosphate uptake in everted intestinal rings (P < 0.01), whereas it had no effect on glucose uptake. The MAS-CM had no effect on either phosphate uptake in the kidney or NPT2 gene promoter activity. In contrast, the CM of the OHO patient significantly inhibited phosphate uptake and NPT2 gene promoter activity. These results indicate that the humoral factor derived from fibrous dysplasia cells of the MAS patient is different to that from OHO patients, because the humoral factor from the MAS patient inhibited phosphate transport not in the kidney but in the intestine."},"publication_date":"2001-09","publication_name":{"en":"Journal of Bone and Mineral Metabolism","ja":"Journal of Bone and Mineral Metabolism"},"volume":"Vol.19","number":"No.5-6","starting_page":"287","ending_page":"295","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/s007740170012"],"issn":["0914-8779"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-17944363928&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=146709","label":"url"}],"paper_title":{"en":"Direct demonstration of humorally mediated inhibition of the transcription of phosphate transporter in XLH patients","ja":"Direct demonstration of humorally mediated inhibition of the transcription of phosphate transporter in XLH patients"},"authors":{"en":[{"name":"Nii Tomoko"},{"name":"Taketani Yutaka"},{"name":"Tani Yoshiko"},{"name":"Ohkido Ichiro"},{"name":"Segawa Hiroko"},{"name":"Yamamoto Hitonori"},{"name":"Morita Kyoko"},{"name":"Minamitani Kanshi"},{"name":"Minagawa Masanori"},{"name":"Yasuda Toshiyuki"},{"name":"Niimi Hiroo"},{"name":"Miyauchi Akimitsu"},{"name":"Miyamoto Ken-ichi"},{"name":"Takeda Eiji"}],"ja":[{"name":"Nii Tomoko"},{"name":"竹谷 豊"},{"name":"Tani Yoshiko"},{"name":"Ohkido Ichiro"},{"name":"瀬川 博子"},{"name":"Yamamoto Hitonori"},{"name":"森田 恭子"},{"name":"Minamitani Kanshi"},{"name":"Minagawa Masanori"},{"name":"Yasuda Toshiyuki"},{"name":"Niimi Hiroo"},{"name":"Miyauchi Akimitsu"},{"name":"宮本 賢一"},{"name":"武田 英二"}]},"publication_date":"2001-09","publication_name":{"en":"Clinical and Experimental Nephrology","ja":"Clinical and Experimental Nephrology"},"volume":"Vol.5","number":"No.3","starting_page":"144","ending_page":"152","referee":true,"identifiers":{"doi":["10.1007/s101570170002"],"issn":["1342-1751"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92149","label":"url"}],"paper_title":{"en":"The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene","ja":"The polymorphism in the caudal-related homeodomain protein Cdx-2 binding element in the human vitamin D receptor gene"},"authors":{"en":[{"name":"Arai Hidekazu"},{"name":"Miyamoto Ken-ichi"},{"name":"Yoshida Michiko"},{"name":"Yamamoto Hironori"},{"name":"Taketani Yutaka"},{"name":"Morita Kyoko"},{"name":"Kubota Megumi"},{"name":"Yoshida Shigeko"},{"name":"Ikeda Mikiko"},{"name":"Watabe F"},{"name":"Kanemasa Y"},{"name":"Takeda Eiji"}],"ja":[{"name":"新井 英一"},{"name":"宮本 賢一"},{"name":"芳田 美智子"},{"name":"山本 浩範"},{"name":"竹谷 豊"},{"name":"森田 恭子"},{"name":"久保田 恵"},{"name":"吉田 繁子"},{"name":"池田 己喜子"},{"name":"Watabe F"},{"name":"Kanemasa Y"},{"name":"武田 英二"}]},"publication_date":"2001-06","publication_name":{"en":"Journal of Bone and Mineral Research","ja":"Journal of Bone and Mineral Research"},"volume":"Vol.16","number":"No.7","starting_page":"1256","ending_page":"1264","languages":["eng"],"referee":true,"identifiers":{"issn":["0884-0431"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0347747812&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92071","label":"url"}],"paper_title":{"en":"Association between two types of vitamin d receptor gene polymorphism and bone status in premenopausal Japanese women.","ja":"Association between two types of vitamin d receptor gene polymorphism and bone status in premenopausal Japanese women."},"authors":{"en":[{"name":"Kubota Megumi"},{"name":"Yoshida Shigeko"},{"name":"Ikeda Mikiko"},{"name":"Okada Y"},{"name":"Arai Hidekazu"},{"name":"Miyamoto Ken-ichi"},{"name":"Takeda Eiji"}],"ja":[{"name":"久保田 恵"},{"name":"吉田 繁子"},{"name":"池田 己喜子"},{"name":"Okada Y"},{"name":"新井 英一"},{"name":"宮本 賢一"},{"name":"武田 英二"}]},"publication_date":"2001-01","publication_name":{"en":"Calcified Tissue International","ja":"Calcified Tissue International"},"volume":"Vol.68","number":"No.1","starting_page":"16","ending_page":"22","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1007/BF02684998"],"issn":["0171-967X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92174","label":"url"}],"paper_title":{"en":"Regulation of intestinal Na+-dependent phosphate co-transporters by a low-phosphate diet and 1,25-dihydroxyvitamin D3.","ja":"Regulation of intestinal Na+-dependent phosphate co-transporters by a low-phosphate diet and 1,25-dihydroxyvitamin D3."},"authors":{"en":[{"name":"Katai Kanako"},{"name":"Miyamoto Ken-ichi"},{"name":"Kishida Sachie"},{"name":"Segawa Hiroko"},{"name":"Nii Tomoko"},{"name":"Tanaka Hiroko"},{"name":"Tani Yoshiko"},{"name":"Arai Hidekazu"},{"name":"Tatsumi Sawako"},{"name":"Morita Kyoko"},{"name":"Taketani Yutaka"},{"name":"Takeda Eiji"}],"ja":[{"name":"片井 加奈子"},{"name":"宮本 賢一"},{"name":"岸田 祐枝"},{"name":"瀬川 博子"},{"name":"新居 智子"},{"name":"田中 裕子"},{"name":"谷 佳子"},{"name":"新井 英一"},{"name":"辰巳 佐和子"},{"name":"森田 恭子"},{"name":"竹谷 豊"},{"name":"武田 英二"}]},"publication_date":"1999-11","publication_name":{"en":"The Journal of Biochemistry","ja":"The Journal of Biochemistry"},"volume":"Vol.343","number":"No.3","starting_page":"705","ending_page":"712","languages":["eng"],"referee":true,"identifiers":{"issn":["0021-924X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/10501287","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92287","label":"url"}],"paper_title":{"en":"Daily pattern of energy metabolism in cirrhosis.","ja":"Daily pattern of energy metabolism in cirrhosis."},"authors":{"en":[{"name":"Okumura Hisami"},{"name":"Genjida Kaori"},{"name":"Yokota Kimi"},{"name":"Taketani Yutaka"},{"name":"Morita Kyoko"},{"name":"Miyamoto Ken-ichi"},{"name":"Miyake Hidenori"},{"name":"Tashiro Seiki"},{"name":"Takeda Eiji"}],"ja":[{"name":"奥村 仙示"},{"name":"源氏田 可織"},{"name":"横田 貴美"},{"name":"竹谷 豊"},{"name":"森田 恭子"},{"name":"宮本 賢一"},{"name":"三宅 秀則"},{"name":"田代 征記"},{"name":"武田 英二"}]},"description":{"en":"The daily pattern of energy expenditure and the oxidation rates of carbohydrates, fats, and protein were evaluated by indirect calorimetry in 18 control subjects (Group 1) and 34 cirrhotic patients who were divided into Groups 2a and 2b showing indocyanin green retention rates at 15 min of <30% and 30% or more, respectively. The ratio of resting energy expenditure to basal energy expenditure (%REE) was higher in the cirrhotic patients than in the controls at 8:30 AM and 2:30 PM. The oxidation rates of carbohydrates and fats under fasting conditions in Group 2b patients were respectively lower, and higher than in Group 1 and 2a patients. After the subjects ate, glucose became the substrate preferentially metabolized, and the proportion of fat metabolized was reduced from 82.9+/-5.1% to 43.9+/-21.9% and from 70.7+/-14.1% to 46.8+/-13.9% in the patients with advanced and less advanced cirrhosis, respectively, and from 59.4+/-27.2% to 48.4+/-18.5% in the controls. The fasting concentrations of non-esterified fatty acids in Group 2b were also significantly higher than those in the Group 1 and Group 2a patients. After eating, these concentrations fell and reached similar levels in the patients and controls. These data indicated that the patients with cirrhosis developed the catabolic state of starvation in the morning because of a lack of glycogen stores. Therefore, frequent meal supplementation to prevent early-onset starvation and energy deficiency may be advisable in such patients to maintain a well-nourished condition.","ja":"The daily pattern of energy expenditure and the oxidation rates of carbohydrates, fats, and protein were evaluated by indirect calorimetry in 18 control subjects (Group 1) and 34 cirrhotic patients who were divided into Groups 2a and 2b showing indocyanin green retention rates at 15 min of <30% and 30% or more, respectively. The ratio of resting energy expenditure to basal energy expenditure (%REE) was higher in the cirrhotic patients than in the controls at 8:30 AM and 2:30 PM. The oxidation rates of carbohydrates and fats under fasting conditions in Group 2b patients were respectively lower, and higher than in Group 1 and 2a patients. After the subjects ate, glucose became the substrate preferentially metabolized, and the proportion of fat metabolized was reduced from 82.9+/-5.1% to 43.9+/-21.9% and from 70.7+/-14.1% to 46.8+/-13.9% in the patients with advanced and less advanced cirrhosis, respectively, and from 59.4+/-27.2% to 48.4+/-18.5% in the controls. The fasting concentrations of non-esterified fatty acids in Group 2b were also significantly higher than those in the Group 1 and Group 2a patients. After eating, these concentrations fell and reached similar levels in the patients and controls. These data indicated that the patients with cirrhosis developed the catabolic state of starvation in the morning because of a lack of glycogen stores. Therefore, frequent meal supplementation to prevent early-onset starvation and energy deficiency may be advisable in such patients to maintain a well-nourished condition."},"publication_date":"1999-10","publication_name":{"en":"Nutrition","ja":"Nutrition"},"volume":"Vol.15","number":"No.10","starting_page":"749","ending_page":"754","languages":["eng"],"referee":true,"identifiers":{"doi":["10.1016/S0899-9007(99)00149-5"],"issn":["0899-9007"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/110667","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/9597809","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0031995075&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92316","label":"url"}],"paper_title":{"en":"Total parenteral nutrition on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation.","ja":"Total parenteral nutrition on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation."},"authors":{"en":[{"name":"Okumura Hisami"},{"name":"Takeda Eiji"},{"name":"Takata Kazumi"},{"name":"Shuto Emi"},{"name":"Miyamoto Ken-ichi"},{"name":"Watanabe Toshiyuki"},{"name":"Kawano Yoshifumi"},{"name":"Takaue Yoichi"},{"name":"Kuroda Yasuhiro"}],"ja":[{"name":"奥村 仙示"},{"name":"武田 英二"},{"name":"高田 和美"},{"name":"首藤 恵泉"},{"name":"宮本 賢一"},{"name":"渡辺 俊之"},{"name":"Kawano Yoshifumi"},{"name":"Takaue Yoichi"},{"name":"黒田 𣳾弘"}]},"description":{"en":"The resting energy expenditure (REE) and the respiratory quotient (RQ) were measured longitudinally using indirect calorimetry to examine the effects of total parenteral nutrition (TPN) on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation (PBSCT). There were six children (two males and four females) and the age ranged from five to 13 years (median, eight yrs). The diagnosis included acute lymphocytic leukemia (ALL; 4), neuroblastoma (NBL; 1) and primitive neuroectodermal tumor (PNET; 1). TPN was started after the patients were stabilized following PBSCT (group A; n = 3) or before the initiation of high-dose cytoreductive chemotherapy (HCC) (group B; n = 3). Duration of HCC before PBSCT was identical between the two groups (six to eight days). Average total calorie and protein intake during HCC was significantly higher for group B than for group A. The %REE, the percentage of REE to the predicted basal energy expenditure (BEE), in group A showed 133 +/- 19%, 129 +/- 14% and 146 +/- 11% during three periods of HCC (days -8 to -1 of PBSCT), bone marrow suppression (days 0 to 11 of PBSCT) and bone marrow recovery (days 12 to 22 of PBSCT), respectively. In contrast, those in group B were 10% to 20% lower than those in group A at all periods. Carbohydrate oxidation rates during HCC in group A were significantly lower than those in group B, and those were not different between both groups during post-PBSCT periods. Fat oxidation rates in both groups were similar at all stages of periods. In contrast, protein degradation rates in group A were significantly higher than those in group B at all stages of the period. From these results, we concluded that commencement of TPN administration prior to HCC in the patients undergoing PBSCT provides beneficial effects to maintain better energy metabolic and nutritional status.","ja":"The resting energy expenditure (REE) and the respiratory quotient (RQ) were measured longitudinally using indirect calorimetry to examine the effects of total parenteral nutrition (TPN) on energy metabolism in children undergoing autologous peripheral blood stem cell transplantation (PBSCT). There were six children (two males and four females) and the age ranged from five to 13 years (median, eight yrs). The diagnosis included acute lymphocytic leukemia (ALL; 4), neuroblastoma (NBL; 1) and primitive neuroectodermal tumor (PNET; 1). TPN was started after the patients were stabilized following PBSCT (group A; n = 3) or before the initiation of high-dose cytoreductive chemotherapy (HCC) (group B; n = 3). Duration of HCC before PBSCT was identical between the two groups (six to eight days). Average total calorie and protein intake during HCC was significantly higher for group B than for group A. The %REE, the percentage of REE to the predicted basal energy expenditure (BEE), in group A showed 133 +/- 19%, 129 +/- 14% and 146 +/- 11% during three periods of HCC (days -8 to -1 of PBSCT), bone marrow suppression (days 0 to 11 of PBSCT) and bone marrow recovery (days 12 to 22 of PBSCT), respectively. In contrast, those in group B were 10% to 20% lower than those in group A at all periods. Carbohydrate oxidation rates during HCC in group A were significantly lower than those in group B, and those were not different between both groups during post-PBSCT periods. Fat oxidation rates in both groups were similar at all stages of periods. In contrast, protein degradation rates in group A were significantly higher than those in group B at all stages of the period. From these results, we concluded that commencement of TPN administration prior to HCC in the patients undergoing PBSCT provides beneficial effects to maintain better energy metabolic and nutritional status."},"publication_date":"1998-02","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.44","number":"No.3-4","starting_page":"199","ending_page":"203","languages":["eng"],"referee":true,"identifiers":{"issn":["1343-1420"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://repo.lib.tokushima-u.ac.jp/ja/111643","label":"url"},{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/9395720","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-0031196541&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92334","label":"url"}],"paper_title":{"en":"Comparison of energy metabolism in insulin-dependent and non-insulin-dependent diabetes mellitus","ja":"Comparison of energy metabolism in insulin-dependent and non-insulin-dependent diabetes mellitus"},"authors":{"en":[{"name":"Takata Kazumi"},{"name":"Chiba Noriko"},{"name":"Tawara Mariko"},{"name":"Okumura Hisami"},{"name":"Shuto Emi"},{"name":"Miyamoto Ken-ichi"},{"name":"Yokota Ichiro"},{"name":"Matsuda Junko"},{"name":"Kuroda Yasuhiro"},{"name":"Takeda Eiji"}],"ja":[{"name":"高田 和美"},{"name":"千葉 紀子"},{"name":"俵 万里子"},{"name":"奥村 仙示"},{"name":"首藤 恵泉"},{"name":"宮本 賢一"},{"name":"横田 一郎"},{"name":"松田 純子"},{"name":"黒田 泰弘"},{"name":"武田 英二"}]},"description":{"en":"To compare the metabolic consequences of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), glycemic control and energy metabolism were evaluated in 18 children displaying IDDM and 19 NIDDM adult patients. With rising concentrations of fasting blood glucose (FBG), hemoglobin A1C and free fatty acid, the percentage of the ratio of resting energy expenditure (REE) to predicted REE expressed as %REE increased and the respiratory quotient (RQ) decreased. The linear regression between RQ and FBG showed the same gradient in IDDM and NIDDM although the RQ in IDDM was always 0.07 lower than that in NIDDM given various FBG concentrations. Those patients whose RQ values were less than 0.7, indicating ketone body production, included 8 (44%) IDDM and 2 (11%) NIDDM patients. These results may explain the relatively greater manifestation of ketoacidosis in IDDM.","ja":"To compare the metabolic consequences of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), glycemic control and energy metabolism were evaluated in 18 children displaying IDDM and 19 NIDDM adult patients. With rising concentrations of fasting blood glucose (FBG), hemoglobin A1C and free fatty acid, the percentage of the ratio of resting energy expenditure (REE) to predicted REE expressed as %REE increased and the respiratory quotient (RQ) decreased. The linear regression between RQ and FBG showed the same gradient in IDDM and NIDDM although the RQ in IDDM was always 0.07 lower than that in NIDDM given various FBG concentrations. Those patients whose RQ values were less than 0.7, indicating ketone body production, included 8 (44%) IDDM and 2 (11%) NIDDM patients. These results may explain the relatively greater manifestation of ketoacidosis in IDDM."},"publication_date":"1997-08","publication_name":{"en":"The Journal of Medical Investigation : JMI","ja":"The Journal of Medical Investigation : JMI"},"volume":"Vol.44","number":"No.1-2","starting_page":"67","ending_page":"71","languages":["eng"],"referee":true,"identifiers":{"issn":["1343-1420"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92197","label":"url"}],"paper_title":{"en":"A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women.","ja":"A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women."},"authors":{"en":[{"name":"Arai Hidekazu"},{"name":"Miyamoto Ken-ichi"},{"name":"Taketani Yutaka"},{"name":"Yamamoto Hironori"},{"name":"Iemori Yuka"},{"name":"Morita Kyoko"},{"name":"Tonai Takeharu"},{"name":"Nishisho Takehiko"},{"name":"Mori Shigenobu"},{"name":"Takeda Eiji"}],"ja":[{"name":"新井 英一"},{"name":"宮本 賢一"},{"name":"竹谷 豊"},{"name":"山本 浩範"},{"name":"家森 由佳"},{"name":"森田 恭子"},{"name":"藤内 武春"},{"name":"西庄"},{"name":"森 しげのぶ"},{"name":"武田 英二"}]},"publication_date":"1997-06","publication_name":{"en":"Journal of Bone and Mineral Research","ja":"Journal of Bone and Mineral Research"},"volume":"Vol.12","number":"No.6","starting_page":"915","ending_page":"921","languages":["eng"],"referee":true,"identifiers":{"issn":["0884-0431"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=92221","label":"url"}],"paper_title":{"en":"Acute regulation by dietary phosphate of the sodium-dependent phosphate transporter (NaP(i)-2) in rat kidney.","ja":"Acute regulation by dietary phosphate of the sodium-dependent phosphate transporter (NaP(i)-2) in rat kidney."},"authors":{"en":[{"name":"Katai Kanako"},{"name":"Segawa Hiroko"},{"name":"Sakata-Haga Hiromi"},{"name":"Morita Kyoko"},{"name":"Arai Hidekazu"},{"name":"Tatsumi Sawako"},{"name":"Taketani Yutaka"},{"name":"Miyamoto Ken-ichi"},{"name":"Hisano Setsuji"},{"name":"Fukui Yoshihiro"},{"name":"Takeda Eiji"}],"ja":[{"name":"片井 加奈子"},{"name":"瀬川 博子"},{"name":"坂田 ひろみ"},{"name":"森田 恭子"},{"name":"新井 英一"},{"name":"辰巳 佐和子"},{"name":"竹谷 豊"},{"name":"宮本 賢一"},{"name":"久野 節二"},{"name":"福井 義浩"},{"name":"武田 英二"}]},"publication_date":"1997-01","publication_name":{"en":"The Journal of Biochemistry","ja":"The Journal of Biochemistry"},"volume":"Vol.121","number":"No.1","starting_page":"50","ending_page":"55","languages":["eng"],"referee":true,"identifiers":{"issn":["0021-924X"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=210204","label":"url"}],"paper_title":{"en":"Vitamin D3 elicits calcium response and activates blood monocyte-derived macrophages from patients with vitamin D dependent rickets type II.","ja":"Vitamin D3 elicits calcium response and activates blood monocyte-derived macrophages from patients with vitamin D dependent rickets type II."},"authors":{"en":[{"name":"Takeda Eiji"},{"name":"Takata K."},{"name":"Yamanaka H."},{"name":"Taketani Yutaka"},{"name":"Morita K."},{"name":"Miyamoto Ken-ichi"},{"name":"Shono Masayuki"},{"name":"Teshima S."},{"name":"Rokutan Kazuhito"}],"ja":[{"name":"武田 英二"},{"name":"Takata K."},{"name":"Yamanaka H."},{"name":"竹谷 豊"},{"name":"Morita K."},{"name":"宮本 賢一"},{"name":"庄野 正行"},{"name":"Teshima S."},{"name":"六反 一仁"}]},"publication_date":"1996-11","publication_name":{"en":"FEBS Letters","ja":"FEBS Letters"},"volume":"Vol.4","number":"No.364","starting_page":"157","ending_page":"160","languages":["eng"],"referee":true,"identifiers":{"issn":["0014-5793"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=161998","label":"url"}],"paper_title":{"en":"Vitamin D3 elicits calcium response and activates blood monocyte-derived macrophages from patients with vitamin D dependent rickets type 2","ja":"Vitamin D3 elicits calcium response and activates blood monocyte-derived macrophages from patients with vitamin D dependent rickets type 2"},"authors":{"en":[{"name":"Takeda Eiji"},{"name":"Takata Kazumi"},{"name":"Yamanaka Hisami"},{"name":"Taketani Yutaka"},{"name":"Morita Kyoko"},{"name":"Miyamoto Ken-ichi"},{"name":"Shono Masayuki"},{"name":"Teshima Shigetada"},{"name":"Rokutan Kazuhito"}],"ja":[{"name":"武田 英二"},{"name":"Takata Kazumi"},{"name":"Yamanaka Hisami"},{"name":"竹谷 豊"},{"name":"森田 恭子"},{"name":"宮本 賢一"},{"name":"Shono Masayuki"},{"name":"手嶋 茂忠"},{"name":"六反 一仁"}]},"publication_date":"1996","publication_name":{"en":"FEBS Letters","ja":"FEBS Letters"},"volume":"Vol.396","starting_page":"157","ending_page":"160","languages":["eng"],"referee":true,"identifiers":{"issn":["0014-5793"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=134926","label":"url"}],"paper_title":{"en":"Vitamin D3 elicits calcium response and activates blood monocyte-derived macrophages from patients with vitamin D dependent rickets type 2","ja":"Vitamin D3 elicits calcium response and activates blood monocyte-derived macrophages from patients with vitamin D dependent rickets type 2"},"authors":{"en":[{"name":"Takeda Eiji"},{"name":"Takata Kazumi"},{"name":"Yamanaka Hisami"},{"name":"Taketani Yutaka"},{"name":"Morita Kyoko"},{"name":"Miyamoto Ken-ichi"},{"name":"Shono Masayuki"},{"name":"Teshima Shigetada"},{"name":"Rokutan Kazuhito"}],"ja":[{"name":"武田 英二"},{"name":"Takata Kazumi"},{"name":"Yamanaka Hisami"},{"name":"竹谷 豊"},{"name":"森田 恭子"},{"name":"宮本 賢一"},{"name":"Shono Masayuki"},{"name":"手嶋 茂忠"},{"name":"六反 一仁"}]},"publication_date":"1996","publication_name":{"en":"FEBS Letters","ja":"FEBS Letters"},"volume":"Vol.396","starting_page":"157","ending_page":"160","languages":["eng"],"referee":true,"identifiers":{"issn":["0014-5793"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://cir.nii.ac.jp/crid/1390574047045835904/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=387834","label":"url"}],"paper_title":{"en":"The physiological function of vitamin D which maintains phosphate homeostasis","ja":"生体内リン恒常性を維持するビタミンD作用"},"authors":{"en":[{"name":"金子 一郎"},{"name":"宇賀 穂"},{"name":"Shiozaki Yuji"},{"name":"Miyamoto Ken-ichi"},{"name":"Segawa Hiroko"}],"ja":[{"name":"金子 一郎"},{"name":"宇賀 穂"},{"name":"塩﨑 雄治"},{"name":"宮本 賢一"},{"name":"瀬川 博子"}]},"description":{"en":"Inorganic phosphate (Pi) plays essential roles in many biological processes. Blood Pi level should be maintained at a constant range because hypophosphatemia causes rickets/osteomalacia, whereas hyperphosphatemia causes cardiovascular events in chronic kidney disease (CKD) or hemodialysis patients. As a phosphaturic hormone, parathyroid hormone (PTH) or fibroblast growth factor (FGF) 23 strongly suppresses Pi reabsorption. 1,25-Dihydroxyvitamin D[1,25(OH) 2D] up-regulates Pi absorption in intestines, and regulates urinary Pi excretion through PTH or FGF23.
Activated FGF23 signal leads urinary Pi excretion, and hypophosphatemic rickets (FGF23-related hypophosphatemic rickets). Rickets characterized as vitamin D deficiency also associates with impaired renal Pi reabsorption in juvenile stage in addition to low Pi absorption in intestines. Now, burosumab (FGF23 neutralizing antibody) has a beneficent effect on FGF23-related hypophosphatemic rickets/osteomalacia. The antibody increases renal Pi reabsorption and 1,25(OH) 2D production. On the other hand, treatment with vitamin D alone in an animal model of X-linked hypophosphatemic rickets can potentially increase renal Pi reabsorption, despite of excess FGF23, and improve hypophosphatemia and bone phenotypes.
CKD patients often accompany with mineral bone disorder (CKD-MBD) such as hyperparathyroidism, cardiovascular calcification, and osteodystrophy. Prevention and treatment for hyperphosphatemia or hypovitaminosis D would improve their QOL or mortality.
Thus, renal Pi reabsorption is important for bone and mineral homeostasis. We focus on the metabolism of Pi and vitamin D to understand the molecular mechanism for the onset and prevention of diseases associated with Pi and vitamin D.","ja":"無機リン酸(リン)は生体内で多くの生化学反応に必要であるため,血中リン濃度は一定範囲内に維持されている.低リン血症はくる病/骨軟化症の原因となり,高リン血症は慢性腎臓病(CKD)や透析患者において心血管疾患発症のリスクファクターとなる.副甲状腺ホルモン(PTH)や線維芽細胞増殖因子23(FGF23)は,腎臓でのリン再吸収を抑制することでリン利尿ホルモンとして機能している.活性型ビタミンD[1,25(OH) 2D]は小腸でのリン吸収を促進することに加え,PTHやFGF23の産生調節も行い,生体内リン恒常性を保っている.
FGF23シグナル活性化は,尿中リン排泄を亢進させ,低リン血症性くる病を引き起こす(FGF23関連低リン血症性くる病).また,ビタミンD依存性くる病では,小腸でのリン吸収抑制に加えて,成長期における尿中リン排泄の亢進が低リン血症の原因となる.近年,FGF23中和抗体(Burosumab)が開発され,腎臓リン再吸収と1,25(OH) 2D産生を改善することでくる病患者に有益な効果を示し,欧米及び日本でFGF23関連低リン血症性くる病・骨軟化症の治療薬として承認されている.一方,X連鎖性低リン血症性くる病モデル動物を用いた実験では,ビタミンD製剤単独投与でも低リン血症性くる病の症状を改善できることが示された.この作用の特徴は,FGF23が高値を示すにも関わらずリン再吸収の改善がみとめられることである.
CKD患者では,しばしば副甲状腺機能亢進や心血管疾患,骨異栄養症など骨ミネラル代謝異常(CKD-MBD: 慢性腎臓病に伴う骨ミネラル代謝異常)が出現する.CKDにおける高リン血症および1,25(OH) 2D低下を予防・治療することで患者のQOLや予後を改善することが報告されている.
このように腎臓でのリン再吸収調節は骨ミネラル代謝に極めて重要である.我々は,リンとビタミンD代謝に注目し,疾患の発症および予防を分子レベルで理解することに努めている."},"publication_date":"2021-06-25","publication_name":{"en":"Vitamins","ja":"ビタミン"},"volume":"Vol.95","number":"No.56","starting_page":"280","ending_page":"285","languages":["jpn"],"identifiers":{"doi":["10.20632/vso.95.5-6_280"],"issn":["0006-386X"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=342315","label":"url"}],"paper_title":{"en":"高リン食の危険性:インスタント食品,加工食品","ja":"高リン食の危険性:インスタント食品,加工食品"},"authors":{"en":[{"name":"Tatsumi Sawako"},{"name":"藤井 理"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"辰巳 佐和子"},{"name":"藤井 理"},{"name":"宮本 賢一"}]},"publication_date":"2017-06-25","publication_name":{"en":"Kidney and Dialysis","ja":"腎と透析"},"volume":"Vol.82","number":"No.6","starting_page":"809","ending_page":"812","languages":["jpn"],"identifiers":{"issn":["0385-2156"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=317078","label":"url"}],"paper_title":{"en":"食餌性リンによる血管障害","ja":"食餌性リンによる血管障害"},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"Taketani Yutaka"}],"ja":[{"name":"宮本 賢一"},{"name":"竹谷 豊"}]},"publication_date":"2015-04-30","publication_name":{"en":"日本透析医会雑誌","ja":"日本透析医会雑誌"},"volume":"Vol.30","number":"No.1","starting_page":"128","ending_page":"133","languages":["jpn"],"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=271075","label":"url"}],"paper_title":{"en":"リン代謝調節機構の分子メカニズム.","ja":"リン代謝調節機構の分子メカニズム."},"authors":{"en":[{"name":"野村 憲吾"},{"name":"塩崎 雄治"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"野村 憲吾"},{"name":"塩崎 雄治"},{"name":"宮本 賢一"}]},"publication_date":"2013-01","publication_name":{"en":"Anual Review腎臓2013","ja":"Anual Review腎臓2013"},"starting_page":"2","ending_page":"16","languages":["jpn"],"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-84866926543&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=271087","label":"url"}],"paper_title":{"en":"Determination of a suitable shear rate for thickened liquids easy for elderly to swallow.","ja":"Determination of a suitable shear rate for thickened liquids easy for elderly to swallow."},"authors":{"en":[{"name":"Yamagata Yoshie"},{"name":"Izumi Ayako"},{"name":"Egashira Fumie"},{"name":"Miyamoto Ken-ichi"},{"name":"Kayashita Jun"}],"ja":[{"name":"Yamagata Yoshie"},{"name":"Izumi Ayako"},{"name":"Egashira Fumie"},{"name":"宮本 賢一"},{"name":"Kayashita Jun"}]},"publication_date":"2012-05","publication_name":{"en":"Food Science and Technology Research","ja":"Food Science and Technology Research"},"volume":"Vol.18","number":"No.3","starting_page":"27","ending_page":"34","languages":["eng"],"identifiers":{"doi":["10.3136/fstr.18.363"],"issn":["1881-3984"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://ci.nii.ac.jp/naid/10030560743/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1572824500599676928/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=271071","label":"url"}],"paper_title":{"en":"The physiological roles of intestinal and renal phosphate transporters : an update","ja":"リン酸トランスポーターをめぐる最近の話題."},"authors":{"en":[{"name":"桑原 煩治"},{"name":"大井 彰子"},{"name":"野村 憲吾"},{"name":"Tatsumi Sawako"},{"name":"Kido Shinsuke"},{"name":"Segawa Hiroko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"桑原 煩治"},{"name":"大井 彰子"},{"name":"野村 憲吾"},{"name":"辰巳 佐和子"},{"name":"木戸 慎介"},{"name":"瀬川 博子"},{"name":"宮本 賢一"}]},"publication_date":"2012-03","publication_name":{"en":"消化と吸収","ja":"消化と吸収"},"volume":"Vol.34","number":"No.3","starting_page":"181","ending_page":"190","languages":["jpn"],"identifiers":{"issn":["0389-3626"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=271066","label":"url"}],"paper_title":{"en":"人体の構造と機能","ja":"人体の構造と機能"},"authors":{"en":[{"name":"加藤 秀夫"},{"name":"中坊 幸弘"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"加藤 秀夫"},{"name":"中坊 幸弘"},{"name":"宮本 賢一"}]},"publication_date":"2012-03-30","publication_name":{"en":"栄養生化学(栄養科学シリーズ)","ja":"栄養生化学(栄養科学シリーズ)"},"languages":["jpn"],"invited":true,"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=254167","label":"url"}],"paper_title":{"en":"リン酸トランスポーターと疾患","ja":"リン酸トランスポーターと疾患"},"authors":{"en":[{"name":"Segawa Hiroko"},{"name":"大井 彰子"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"瀬川 博子"},{"name":"大井 彰子"},{"name":"宮本 賢一"}]},"publication_date":"2011-10-10","publication_name":{"en":"Bio Clinica 腎臓トランスポーター異常による疾患","ja":"Bio Clinica 腎臓トランスポーター異常による疾患"},"volume":"Vol.Vol26","number":"No.No11","starting_page":"23","ending_page":"27","languages":["jpn"],"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21741473","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=254134","label":"url"}],"paper_title":{"en":"Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats.","ja":"Accumulation of orally administered quercetin in brain tissue and its antioxidative effects in rats."},"authors":{"en":[{"name":"Ishisaka Akari"},{"name":"Ichikawa Satomi"},{"name":"Sakakibara Hiroyuki"},{"name":"Piskula Mariusz K"},{"name":"Nakamura Toshiyuki"},{"name":"Kato Yoji"},{"name":"Ito Mikiko"},{"name":"Miyamoto Ken-ichi"},{"name":"Tsuji Akira"},{"name":"Kawai Yoshichika"},{"name":"Terao Junji"}],"ja":[{"name":"Ishisaka Akari"},{"name":"Ichikawa Satomi"},{"name":"Sakakibara Hiroyuki"},{"name":"Piskula Mariusz K"},{"name":"Nakamura Toshiyuki"},{"name":"Kato Yoji"},{"name":"伊藤 美紀子"},{"name":"宮本 賢一"},{"name":"Tsuji Akira"},{"name":"Kawai Yoshichika"},{"name":"寺尾 純二"}]},"description":{"en":"Quercetin is widely distributed in vegetables and herbs and has been suggested to act as a neuroprotective agent. Here, we demonstrate that quercetin can accumulate enough to exert biological activity in rat brain tissues. Homogenates of perfused rat brain without detectable hemoglobin contaminants were treated with -glucuronidase/sulfatase and the released quercetin and its methylated form were analyzed using high-performance liquid chromatography (HPLC) with three different detection methods. Both quercetin and the methylated form were detected in the brain of quercetin-administered rats using HPLC-UV and HPLC with electrochemical detection and were further identified using HPLC-tandem mass spectrometry. Oral administration of quercetin (50mg/kg body wt) attenuated the increased oxidative stress in the hippocampus and striatum of rats exposed to chronic forced swimming. The possible transport of quercetin derivatives into the brain tissue was reproduced in vitro by using a rat brain capillary endothelial cell line, a model of the blood-brain barrier. These results show that quercetin could be a potent nutrient that can access the brain and protect it from disorders associated with oxidative stress.","ja":"Quercetin is widely distributed in vegetables and herbs and has been suggested to act as a neuroprotective agent. Here, we demonstrate that quercetin can accumulate enough to exert biological activity in rat brain tissues. Homogenates of perfused rat brain without detectable hemoglobin contaminants were treated with -glucuronidase/sulfatase and the released quercetin and its methylated form were analyzed using high-performance liquid chromatography (HPLC) with three different detection methods. Both quercetin and the methylated form were detected in the brain of quercetin-administered rats using HPLC-UV and HPLC with electrochemical detection and were further identified using HPLC-tandem mass spectrometry. Oral administration of quercetin (50mg/kg body wt) attenuated the increased oxidative stress in the hippocampus and striatum of rats exposed to chronic forced swimming. The possible transport of quercetin derivatives into the brain tissue was reproduced in vitro by using a rat brain capillary endothelial cell line, a model of the blood-brain barrier. These results show that quercetin could be a potent nutrient that can access the brain and protect it from disorders associated with oxidative stress."},"publication_date":"2011-06-23","publication_name":{"en":"Free Radical Biology and Medicine","ja":"Free Radical Biology and Medicine"},"volume":"Vol.51","number":"No.7","starting_page":"1329","ending_page":"1336","languages":["eng"],"identifiers":{"doi":["10.1016/j.freeradbiomed.2011.06.017"],"issn":["1873-4596"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=254156","label":"url"}],"paper_title":{"en":"ペプチドトランスポーターの機能と生理作用","ja":"ペプチドトランスポーターの機能と生理作用"},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"古谷 順也"},{"name":"桑原 頌冶"},{"name":"大井 彰子"},{"name":"Segawa Hiroko"}],"ja":[{"name":"宮本 賢一"},{"name":"古谷 順也"},{"name":"桑原 頌冶"},{"name":"大井 彰子"},{"name":"瀬川 博子"}]},"publication_date":"2011-05-10","publication_name":{"en":"栄養・食品機能とトランスポーター","ja":"栄養・食品機能とトランスポーター"},"starting_page":"63","ending_page":"80","languages":["jpn"],"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=254188","label":"url"}],"paper_title":{"en":"リン摂取の危険性","ja":"リン摂取の危険性"},"authors":{"en":[{"name":"大井 彰子"},{"name":"野村 憲吾"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"大井 彰子"},{"name":"野村 憲吾"},{"name":"宮本 賢一"}]},"publication_date":"2011","publication_name":{"en":"Clinical Calcium","ja":"Clinical Calcium"},"volume":"Vol.Vol21","number":"No.o12","starting_page":"171","ending_page":"174","languages":["jpn"],"identifiers":{"issn":["0917-5857"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/21697632","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=254119","label":"url"}],"paper_title":{"en":"Dietary medium-chain triglycerides attenuate hepatic lipid deposition in growing rats with protein malnutrition.","ja":"Dietary medium-chain triglycerides attenuate hepatic lipid deposition in growing rats with protein malnutrition."},"authors":{"en":[{"name":"Kuwahata Masashi"},{"name":"Kubota Hiroyo"},{"name":"Amano Saki"},{"name":"Yokoyama Meiko"},{"name":"Shimamura Yasuhiro"},{"name":"Ito Shunsuke"},{"name":"Ogawa Aki"},{"name":"Kobayashi Yukiko"},{"name":"Miyamoto Ken-ichi"},{"name":"Kido Yasuhiro"}],"ja":[{"name":"桑波田 雅士"},{"name":"Kubota Hiroyo"},{"name":"Amano Saki"},{"name":"Yokoyama Meiko"},{"name":"Shimamura Yasuhiro"},{"name":"Ito Shunsuke"},{"name":"Ogawa Aki"},{"name":"Kobayashi Yukiko"},{"name":"宮本 賢一"},{"name":"Kido Yasuhiro"}]},"description":{"en":"The objective of this study was to investigate the effects of dietary medium-chain triglycerides (MCT) on hepatic lipid accumulation in growing rats with protein malnutrition. Weaning rats were fed either a low-protein diet (3%, LP) or control protein diet (20%, CP), in combination with or without MCT. The four groups were as follows: CP-MCT, CP+MCT, LP-MCT, and LP+MCT. Rats in the CP-MCT, CP+MCT and LP+MCT groups were pair-fed their respective diets based on the amount of diet consumed by the LP-MCT group. Rats were fed each experimental diet for 30 d. Four weeks later, the respiratory quotient was higher in the LP-MCT group than those in the other groups during the fasting period. Hepatic triglyceride content increased in the LP groups compared with the CP groups. Hepatic triglyceride content in the LP+MCT group, however, was significantly decreased compared with that in the LP-MCT group. Levels of carnitine palmitoyltransferase (CPT) 1a mRNA and CPT2 mRNA were significantly decreased in the livers of the LP-MCT group, as compared with corresponding mRNA levels of the other groups. These results suggest that ingestion of a low-protein diet caused fatty liver in growing rats. However, when rats were fed the low-protein diet with MCT, hepatic triglyceride deposition was attenuated, and mRNA levels encoding CPT1a and CPT2 were preserved at the levels of rats fed control protein diets.","ja":"The objective of this study was to investigate the effects of dietary medium-chain triglycerides (MCT) on hepatic lipid accumulation in growing rats with protein malnutrition. Weaning rats were fed either a low-protein diet (3%, LP) or control protein diet (20%, CP), in combination with or without MCT. The four groups were as follows: CP-MCT, CP+MCT, LP-MCT, and LP+MCT. Rats in the CP-MCT, CP+MCT and LP+MCT groups were pair-fed their respective diets based on the amount of diet consumed by the LP-MCT group. Rats were fed each experimental diet for 30 d. Four weeks later, the respiratory quotient was higher in the LP-MCT group than those in the other groups during the fasting period. Hepatic triglyceride content increased in the LP groups compared with the CP groups. Hepatic triglyceride content in the LP+MCT group, however, was significantly decreased compared with that in the LP-MCT group. Levels of carnitine palmitoyltransferase (CPT) 1a mRNA and CPT2 mRNA were significantly decreased in the livers of the LP-MCT group, as compared with corresponding mRNA levels of the other groups. These results suggest that ingestion of a low-protein diet caused fatty liver in growing rats. However, when rats were fed the low-protein diet with MCT, hepatic triglyceride deposition was attenuated, and mRNA levels encoding CPT1a and CPT2 were preserved at the levels of rats fed control protein diets."},"publication_date":"2011","publication_name":{"en":"Journal of Nutritional Science and Vitaminology","ja":"Journal of Nutritional Science and Vitaminology"},"volume":"Vol.57","number":"No.2","starting_page":"138","ending_page":"143","languages":["eng"],"identifiers":{"doi":["10.3177/jnsv.57.138"],"issn":["1881-7742"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://cir.nii.ac.jp/crid/1010000782037286160/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=234370","label":"url"}],"paper_title":{"en":"腎臓と骨代謝関連ホルモン","ja":"腎臓と骨代謝関連ホルモン"},"authors":{"en":[{"name":"金子 一郎"},{"name":"杉野 紗貴子"},{"name":"Segawa Hiroko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"金子 一郎"},{"name":"杉野 紗貴子"},{"name":"瀬川 博子"},{"name":"宮本 賢一"}]},"publication_date":"2010-10","publication_name":{"en":"THE BONE","ja":"THE BONE"},"volume":"Vol.24","number":"No.4","starting_page":"55","ending_page":"58","languages":["jpn"],"identifiers":{"issn":["0914-7047"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=234366","label":"url"}],"paper_title":{"en":"フォスファトニンとリン","ja":"フォスファトニンとリン"},"authors":{"en":[{"name":"Miyamoto Ken-ichi"},{"name":"山口 誠一"},{"name":"Tatsumi Sawako"},{"name":"Kido Shinsuke"},{"name":"Segawa Hiroko"}],"ja":[{"name":"宮本 賢一"},{"name":"山口 誠一"},{"name":"辰巳 佐和子"},{"name":"木戸 慎介"},{"name":"瀬川 博子"}]},"publication_date":"2010-08","publication_name":{"en":"腎と透析","ja":"腎と透析"},"volume":"Vol.69","number":"No.2","starting_page":"200","ending_page":"202","languages":["jpn"],"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://www.ncbi.nlm.nih.gov/pubmed/16985213","label":"url"},{"@id":"https://www.scopus.com/record/display.url?eid=2-s2.0-33846867744&origin=inward","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=161995","label":"url"}],"paper_title":{"en":"Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice.","ja":"Correlation between hyperphosphatemia and type II Na-Pi cotransporter activity in klotho mice."},"authors":{"en":[{"name":"Segawa Hiroko"},{"name":"Yamanaka Setsuko"},{"name":"Ohno Yasue"},{"name":"Onitsuka Akemi"},{"name":"Shiozawa Kazuyo"},{"name":"Aranami Fumito"},{"name":"Furutani Junya"},{"name":"Tomoe Yuka"},{"name":"Ito Mikiko"},{"name":"Kuwahata Masashi"},{"name":"Imura Akihiro"},{"name":"Nabeshima Yoichi"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"Segawa Hiroko"},{"name":"Yamanaka Setsuko"},{"name":"Ohno Yasue"},{"name":"Onitsuka Akemi"},{"name":"Shiozawa Kazuyo"},{"name":"Aranami Fumito"},{"name":"Furutani Junya"},{"name":"Tomoe Yuka"},{"name":"Ito Mikiko"},{"name":"Kuwahata Masashi"},{"name":"Imura Akihiro"},{"name":"Nabeshima Yoichi"},{"name":"宮本 賢一"}]},"description":{"en":"Recent studies have demonstrated that klotho protein plays a role in calcium/phosphate homeostasis. The goal of the present study was to investigate the regulation of Na-P(i) cotransporters in klotho mutant (kl/kl) mice. The kl/kl mice displayed hyperphosphatemia, high plasma 1,25(OH)(2)D(3) levels, increased activity of the renal and intestinal sodium-dependent P(i) cotransporters, and increased levels of the type IIa, type IIb, and type IIc transporter proteins compared with wild-type mice. Interestingly, transcript levels of the type IIa/type IIc transporter mRNA abundance, but not transcripts levels of type IIb transporter mRNA, were markedly decreased in kl/kl mice compared with wild-type mice. Furthermore, plasma fibroblast growth factor 23 (FGF23) levels were 150-fold higher in kl/kl mice than in wild-type mice. Feeding of a low-P(i) diet induced the expression of klotho protein and decreased plasma FGF23 levels in kl/kl mice, whereas colchicine treatment experiments revealed evidence of abnormal membrane trafficking of the type IIa transporter in kl/kl mice. Finally, feeding of a low-P(i) diet resulted in increased type IIa Na-P(i) cotransporter protein in the apical membrane in the wild-type mice, but not in kl/kl mice. These results indicate that hyperphosphatemia in klotho mice is due to dysregulation of expression and trafficking of the renal type IIa/IIc transporters rather than to intestinal P(i) uptake.","ja":"Recent studies have demonstrated that klotho protein plays a role in calcium/phosphate homeostasis. The goal of the present study was to investigate the regulation of Na-P(i) cotransporters in klotho mutant (kl/kl) mice. The kl/kl mice displayed hyperphosphatemia, high plasma 1,25(OH)(2)D(3) levels, increased activity of the renal and intestinal sodium-dependent P(i) cotransporters, and increased levels of the type IIa, type IIb, and type IIc transporter proteins compared with wild-type mice. Interestingly, transcript levels of the type IIa/type IIc transporter mRNA abundance, but not transcripts levels of type IIb transporter mRNA, were markedly decreased in kl/kl mice compared with wild-type mice. Furthermore, plasma fibroblast growth factor 23 (FGF23) levels were 150-fold higher in kl/kl mice than in wild-type mice. Feeding of a low-P(i) diet induced the expression of klotho protein and decreased plasma FGF23 levels in kl/kl mice, whereas colchicine treatment experiments revealed evidence of abnormal membrane trafficking of the type IIa transporter in kl/kl mice. Finally, feeding of a low-P(i) diet resulted in increased type IIa Na-P(i) cotransporter protein in the apical membrane in the wild-type mice, but not in kl/kl mice. These results indicate that hyperphosphatemia in klotho mice is due to dysregulation of expression and trafficking of the renal type IIa/IIc transporters rather than to intestinal P(i) uptake."},"publication_date":"2006-09-19","publication_name":{"en":"American Journal of Physiology, Renal Physiology","ja":"American Journal of Physiology, Renal Physiology"},"volume":"Vol.292","number":"No.2","starting_page":"F769","ending_page":"F779","languages":["eng"],"identifiers":{"doi":["10.1152/ajprenal.00248.2006"],"issn":["1931-857X"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"http://ci.nii.ac.jp/naid/40006665521/","label":"url"},{"@id":"https://cir.nii.ac.jp/crid/1520010380897734784/","label":"url"},{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=130368","label":"url"}],"paper_title":{"en":"Posttranscriptional Regulation of Albumin Gene Expression in Rats with Acute Liver Injury:Effect of Branched-Chain Amino Acids on Its Regulation","ja":"肝障害モデルラットのアルブミン遺伝子転写後調節機構と分岐鎖アミノ酸製剤"},"authors":{"en":[{"name":"Kuwahata Masashi"},{"name":"Segawa Hiroko"},{"name":"Ito Mikiko"},{"name":"Miyamoto Ken-ichi"}],"ja":[{"name":"桑波田 雅士"},{"name":"瀬川 博子"},{"name":"伊藤 美紀子"},{"name":"宮本 賢一"}]},"publication_date":"2005-02","publication_name":{"en":"Reports of the Research Committee of Essential Amino Acids (Japan)","ja":"必須アミノ酸研究"},"number":"No.172","starting_page":"45","ending_page":"50","languages":["jpn"],"identifiers":{"issn":["0387-4141"]},"published_paper_type":"research_institution"},"priority":"input_data"}
{"insert":{"type":"published_papers"},"similar_merge":{"see_also":[{"@id":"https://web.db.tokushima-u.ac.jp/cgi-bin/edb_browse?EID=210181","label":"url"}],"paper_title":{"en":"Ornithine decarboxylase (ODC)の高感度測定の試み","ja":"Ornithine decarboxylase (ODC)の高感度測定の試み"},"authors":{"en":[{"name":"Shono Masayuki"},{"name":"Miyamoto Ken-ichi"},{"name":"多田 千代美"},{"name":"松原 智子"},{"name":"藤井 尊"}],"ja":[{"name":"庄野 正行"},{"name":"宮本 賢一"},{"name":"多田 千代美"},{"name":"松原 智子"},{"name":"藤井 尊"}]},"publication_date":"1992","publication_name":{"en":"Journal of Medical Technology","ja":"臨床検査"},"volume":"Vol.36","number":"No.6","starting_page":"685","ending_page":"686","languages":["jpn"],"identifiers":{"issn":["0485-1420"]},"published_paper_type":"scientific_journal"},"priority":"input_data"}