shiozaki_y/published_papers/46958171 Minori Uga Ichiro Kaneko Yuji Shiozaki Megumi Koike Naoko Tsugawa Peter W Jurutka Ken-Ichi Miyamoto Hiroko Segawa The Role of Intestinal Cytochrome P450s in Vitamin D Metabolism. Vitamin D hydroxylation in the liver/kidney results in conversion to its physiologically active form of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. 1,25(OH)2D3 controls gene expression through the nuclear vitamin D receptor (VDR) mainly expressed in intestinal epithelial cells. Cytochrome P450 (CYP) 24A1 is a catabolic enzyme expressed in the kidneys. Interestingly, a recently identified mutation in another CYP enzyme, CYP3A4 (gain-of-function), caused type III vitamin D-dependent rickets. CYP3A are also expressed in the intestine, but their hydroxylation activities towards vitamin D substrates are unknown. We evaluated CYP3A or CYP24A1 activities on vitamin D action in cultured cells. In addition, we examined the expression level and regulation of CYP enzymes in intestines from mice. The expression of CYP3A or CYP24A1 significantly reduced 1,25(OH)2D3-VDRE activity. Moreover, in mice, Cyp24a1 mRNA was significantly induced by 1,25(OH)2D3 in the intestine, but a mature form (approximately 55 kDa protein) was also expressed in mitochondria and induced by 1,25(OH)2D3, and this mitochondrial enzyme appears to hydroxylate 25OHD3 to 24,25(OH)2D3. Thus, CYP3A or CYP24A1 could locally attenuate 25OHD3 or 1,25(OH)2D3 action, and we suggest the small intestine is both a vitamin D target tissue, as well as a newly recognized vitamin D-metabolizing tissue. Biomolecules 14 6 null null 20240617 10.3390/biom14060717 38927120 shiozaki_y/published_papers/46680126 Megumi Koike Tetsuhiko Sato Yuji Shiozaki Aoi Komiya Mizuki Miura Ayami Higashi Akane Ishikawa Kaori Takayanagi Minori Uga Ken-Ichi Miyamoto Hiroko Segawa Involvement of α-klotho in growth hormone (GH) signaling. Growth hormone (GH) exerts multiple effects on different organs directly or via its main mediator, insulin-like growth factor1 (IGF1). In this study, we focused on the novel relationship between GH action and the antiaging hormone α-klotho. Immunofluorescent staining of α-klotho was observed in the renal distal tubules and pituitary glands of somatostatin- and GH-positive cells in wild-type (WT) mice. Treatment of 4-week-old WT mice with GH increased IGF1 mRNA expression in the pituitary gland, liver, heart, kidney, and bone but increased α-klotho mRNA expression only in the pituitary gland, kidney, and bone. Increased α-klotho protein levels were observed in the kidney but not in the pituitary gland. No induction of α-klotho RNA expression by GH was observed in juvenile mice with kidney disease, indicating GH resistance. Furthermore, GH and α-klotho supplementation in HEK293 cells transfected with GHR increased Janus kinase 2 mRNA (a GH downstream signal) expression compared to supplementation with GH alone. In conclusion, we suggest that 1) the kidney is the main source of secreted α-klotho, which is detected in blood by the downstream action of GH, 2) α-klotho induction by GH is resistant in kidney disease, and 3) α-klotho might be an enhanced regulator of GH signaling. Journal of clinical biochemistry and nutrition 74 3 221 229 20240500 10.3164/jcbn.23-127 38799134 shiozaki_y/published_papers/46230945 Shinobu Miyazaki-Anzai Masashi Masuda Audrey L Keenan Yuji Shiozaki Jose G Miranda Makoto Miyazaki Activation of the IKK2/NF-κB pathway in VSMCs inhibits calcified vascular stiffness in CKD. IKK2/NF-κB pathway-mediated inflammation in vascular smooth muscle cells (VSMCs) has been proposed to be an etiologic factor in medial calcification and stiffness. However, the role of the IKK2/NF-κB pathway in medial calcification remains to be elucidated. In this study, we found that chronic kidney disease (CKD) induces inflammatory pathways through the local activation of the IKK2/NF-κB pathway in VMSCs associated with calcified vascular stiffness. Despite reducing the expression of inflammatory mediators, complete inhibition of the IKK2/NF-κB pathway in vitro and in vivo unexpectedly exacerbated vascular mineralization and stiffness. In contrast, activation of NF-κB by SMC-specific IκBα deficiency attenuated calcified vascular stiffness in CKD. Inhibition of the IKK2/NF-κB pathway induced cell death of VSMCs by reducing anti-cell death gene expression, whereas activation of NF-κB reduced CKD-dependent vascular cell death. In addition, increased calcification of extracellular vesicles through the inhibition of the IKK2/NF-κB pathway induced mineralization of VSMCs, which was significantly reduced by blocking cell death in vitro and in vivo. This study reveals that activation of the IKK2/NF-κB pathway in VSMCs plays a protective role in CKD-dependent calcified vascular stiffness by reducing the release of apoptotic calcifying extracellular vesicles. JCI insight 9 7 null null 20240408 10.1172/jci.insight.174977 38470493 shiozaki_y/published_papers/46713798 小池 萌 東 彩生 小宮 蒼 塩﨑 雄治 瀬川 博子 特集 CKD患者の栄養管理update 病態を考慮した栄養介入の実際 リン管理-CKD-MBDと栄養 東京医学社 腎と透析 0385-2156 96 1 112 116 20240125 10.24479/kd.0000001175 1390580793827920896 shiozaki_y/published_papers/46713795 小池 萌 塩崎 雄治 瀬川 博子 特集 CKD-MBDの新しい潮流 CKD-MBDの病態 無機リン酸の恒常性維持 東京医学社 腎と透析 0385-2156 95 3 267 271 20230925 10.24479/kd.0000000864 1390860620061733888 shiozaki_y/published_papers/42302344 Kazuya Tanifuji Yuji Shiozaki Megumi Koike Minori Uga Aoi Komiya Mizuki Miura Ayami Higashi Takaaki Shimohata Akira Takahashi Noriko Ishizuka Hisayoshi Hayashi Yasuhiro Ichida Shuichi Ohtomo Naoshi Horiba Ken-Ichi Miyamoto Hiroko Segawa Effects of EOS789, a novel pan-phosphate transporter inhibitor, on phosphate metabolism : Comparison with a conventional phosphate binder. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. The journal of medical investigation : JMI 70 1.2 260 270 20230000 10.2152/jmi.70.260 37164731 shiozaki_y/published_papers/46713800 谷藤 和也 小池 萌 宇賀 稔 塩崎 雄治 瀬川 博子 特集 腎臓の自動制御機構 【各論】 Ca,Pホメオスタシス 東京医学社 腎と透析 0385-2156 93 5 736 741 20221125 10.24479/kd.0000000375 1390577133295330048 shiozaki_y/published_papers/49218504 佐々木 すみれ 塩崎 雄治 小池 萌 谷藤 和也 宇賀 穂 Wiriyasermkul Pattama 長谷川 智香 網塚 憲生 宮本 賢一 永森 收志 金井 好克 瀬川 博子 Tmem174はリン酸トランスポーターを調節し高リン血症を予防する (公社)日本生化学会 日本生化学会大会プログラム・講演要旨集 95 1T08a 08 20221100 shiozaki_y/published_papers/40943751 瀬川 博子 塩崎 雄治 小池 萌 宮本 賢一 骨ミネラル代謝の新知見 リン酸バランスの生理学 (一社)日本腎臓学会 日本腎臓学会誌 1884-0728 64 3 209 209 20220500 shiozaki_y/published_papers/40943748 瀬川 博子 塩崎 雄治 金子 一郎 宮本 賢一 ミネラルの新機能 リンが関する生体機能 成長，疾患，寿命 (公社)日本栄養・食糧学会 日本栄養・食糧学会大会講演要旨集 76 148 148 20220500 shiozaki_y/published_papers/37726800 Sumire Sasaki Yuji Shiozaki Ai Hanazaki Megumi Koike Kazuya Tanifuji Minori Uga Kota Kawahara Ichiro Kaneko Yasuharu Kawamoto Pattama Wiriyasermkul Tomoka Hasegawa Norio Amizuka Ken-ichi Miyamoto Shushi Nagamori Yoshikatsu Kanai Hiroko Segawa Tmem174, a regulator of phosphate transporter prevents hyperphosphatemia Abstract 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. Springer Science and Business Media LLC Scientific Reports 2045-2322 12 1 6353 6353 20220500 10.1038/s41598-022-10409-3 35428804 shiozaki_y/published_papers/40943753 周 俊先 大河内 善史 水谷 夏希 塩崎 雄治 瀬川 博子 岡村 康司 腎臓で機能するNa-Pi cotransporter SLC34A3のイオン輸送の仕組みの解明 (一社)日本生理学会 日本生理学雑誌 0031-9341 84 1 33 33 20220200 shiozaki_y/published_papers/40746199 Sumire Sasaki Megumi Koike Kazuya Tanifuji Minori Uga Kota Kawahara Aoi Komiya Mizuki Miura Yamato Harada Yuki Hamaguchi Shohei Sasaki Yuji Shiozaki Ichiro Kaneko Ken-Ichi Miyamoto Hiroko Segawa Dietary polyphosphate has a greater effect on renal damage and FGF23 secretion than dietary monophosphate. 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. The journal of medical investigation : JMI 69 3.4 173 179 20220000 10.2152/jmi.69.173 36244766 shiozaki_y/published_papers/40943756 金子 一郎 宇賀 穂 塩崎 雄治 宮本 賢一 瀬川 博子 【「ビタミン・バイオファクター研究の新潮流」(第72回大会 若手シンポジウム)】生体内リン恒常性を維持するビタミンD作用 低リン血症はくる病発症，高リン血症は特に慢性腎臓病における心血管疾患発症のリスクファクターとなる．生体内リン恒常性は副甲状腺ホルモン，線維芽細胞増殖因子23/αクロトー，ビタミンDを中心とした多臓器連関によるリン独自のシグナルによって保たれている．生体内リンバランスを維持するためのビタミンD作用を中心に，以下の項目に分けて概説した．1)生体内リン恒常性調節，2)ビタミンD代謝と作用機序，3)リン代謝破綻関連疾患，として述べた． (公社)日本ビタミン学会 ビタミン 0006-386X 95 5-6 280 285 20210600 shiozaki_y/published_papers/37654401 Shinobu Miyazaki-Anzai Masashi Masuda Yuji Shiozaki Audrey L Keenan Michel Chonchol Claus Kremoser Makoto Miyazaki Free Deoxycholic Acid Exacerbates Vascular Calcification in CKD through ER Stress-Mediated ATF4 Activation. Background: Our metabolome approach found that levels of circulating, free deoxycholic acid (DCA) is associated with the severity of vascular calcification in patients with CKD. However, it is not known whether DCA directly causes vascular calcification in CKD. Methods: Using various chemicals and animal and cell culture models, we investigated whether the modulation of DCA levels influences vascular calcification in CKD. Results: CKD increased levels of DCA in mice and humans by decreasing urinary DCA excretion. Treatment of cultured VSMCs with DCA but no other bile acids (BAs) induced vascular calcification and osteogenic differentiation through endoplasmic reticulum (ER) stress-mediated activating transcription factor-4 (ATF4) activation. Treatment of mice with Farnesoid X receptor (FXR)-specific agonists selectively reduced levels of circulating cholic acid-derived BAs, such as DCA, protecting from CKD-dependent medial calcification and atherosclerotic calcification. Reciprocal FXR deficiency and DCA treatment induced vascular calcification by increasing levels of circulating DCA and activating the ER stress response. Conclusions: This study demonstrates that DCA plays a causative role in regulating CKD-dependent vascular diseases through ER stress-mediated ATF4 activation. Kidney360 2 5 857 868 20210500 10.34067/kid.0007502020 34423309 shiozaki_y/published_papers/32165806 Yuji Shiozaki Shinobu Miyazaki-Anzai Kayo Okamura Audrey L Keenan Masashi Masuda Makoto Miyazaki GPAT4-Generated Saturated LPAs Induce Lipotoxicity through Inhibition of Autophagy by Abnormal Formation of Omegasomes. Excessive levels of saturated fatty acids are toxic to vascular smooth muscle cells (VSMCs). We previously reported that mice lacking VSMC-stearoyl-CoA desaturase (SCD), a major enzyme catalyzing the detoxification of saturated fatty acids, develop severe vascular calcification from the massive accumulation of lipid metabolites containing saturated fatty acids. However, the mechanism by which SCD deficiency causes vascular calcification is not completely understood. Here, we demonstrate that saturated fatty acids significantly inhibit autophagic flux in VSMCs, contributing to vascular calcification and apoptosis. Mechanistically, saturated fatty acids are accumulated as saturated lysophosphatidic acids (LPAs) (i.e. 1-stearoyl-LPA) possibly synthesized through the reaction of GPAT4 at the contact site between omegasomes and the MAM. The accumulation of saturated LPAs at the contact site causes abnormal formation of omegasomes, resulting in accumulation of autophagosomal precursor isolation membranes, leading to inhibition of autophagic flux. Thus, saturated LPAs are major metabolites mediating autophagy inhibition and vascular calcification. iScience 23 5 101105 101105 20200522 10.1016/j.isci.2020.101105 32408172 shiozaki_y/published_papers/32165808 Ai Hanazaki Kayo Ikuta Shohei Sasaki Sumire Sasaki Megumi Koike Kazuya Tanifuji Yuki Arima Ichiro Kaneko Yuji Shiozaki Sawako Tatsumi Tomoka Hasegawa Norio Amizuka Ken-Ichi Miyamoto Hiroko Segawa Role of sodium-dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages. SLC34A3/NPT2c/NaPi-2c/Npt2c is a growth-related NaPi cotransporter that mediates the uptake of renal sodium-dependent phosphate (Pi). Mutation of human NPT2c causes hereditary hypophosphatemic rickets with hypercalciuria. Mice with Npt2c knockout, however, exhibit normal Pi metabolism. To investigate the role of Npt2c in Pi homeostasis, we generated α-klotho-/- /Npt2c-/- (KL2cDKO) mice and analyzed Pi homeostasis. α-Klotho-/- (KLKO) mice exhibit hyperphosphatemia and markedly increased kidney Npt2c protein levels. Genetic disruption of Npt2c extended the lifespan of KLKO mice similar to that of α-Klotho-/- /Npt2a-/- mice. Adult KL2cDKO mice had hyperphosphatemia, but analysis of Pi metabolism revealed significantly decreased intestinal and renal Pi (re)absorption compared with KLKO mice. The 1,25-dihydroxy vitamin D3 concentration was not reduced in KL2cDKO mice compared with that in KLKO mice. The KL2cDKO mice had less severe soft tissue and vascular calcification compared with KLKO mice. Juvenile KL2cDKO mice had significantly reduced plasma Pi levels, but Pi metabolism was not changed. In Npt2cKO mice, plasma Pi levels began to decrease around the age of 15 days and significant hypophosphatemia developed within 21 days. The findings of the present study suggest that Npt2c contributes to regulating plasma Pi levels in the juvenile stage and affects Pi retention in the soft and vascular tissues in KLKO mice. Physiological reports 8 3 e14324 null 20200200 10.14814/phy2.14324 32026654 shiozaki_y/published_papers/32165810 Toru Fujii Hiroko Segawa Ai Hanazaki Shiori Nishiguchi Sakura Minoshima Akiko Ohi Rieko Tominaga Sumire Sasaki Kazuya Tanifuji Megumi Koike Yuki Arima Yuji Shiozaki Ichiro Kaneko Mikiko Ito Sawako Tatsumi Ken-Ichi Miyamoto Role of the putative PKC phosphorylation sites of the type IIc sodium-dependent phosphate transporter in parathyroid hormone regulation. BACKGROUND: Injection of parathyroid hormone (PTH) rapidly stimulates renal Pi excretion, in part by downregulating NaPi-IIa (Npt2a/SLC34A1) and NaPi-IIc (Npt2c/SLC34A3) transporters. The mechanisms underlying the effects of PTH on NaPi-IIc are not fully elucidated. METHODS: We analyzed the effect of PTH on inorganic phosphate (Pi) reabsorption in Npt2a-/- mice to eliminate the influence of Npt2a on renal Pi reabsorption. In opossum kidney (OK) cells and Xenopus oocytes, we investigated the effect of NaPi-IIc transporter phosphorylation. Studies of mice with mutations of NaPi-IIc protein in which serine and threonine were replaced with either alanine (A), which prevents phosphorylation, or aspartic acid (D), which mimics the charged state of phosphorylated NaPi-IIc, were also performed to evaluate the involvement of phosphorylation in the regulation of transport function. RESULTS: The Npt2a-/- experiments showed that PTH administration rapidly inactivated NaPi-IIc function in the apical membrane of proximal tubular cells. Analysis of mutant proteins (S71, S138, T151, S174, T583) at putative protein kinase C sites, revealed that S138 markedly suppressed the function and cellular expression of mouse NaPi-IIc in Xenopus oocytes and OK cells. In addition, 138D had a short half-life compared with wild-type protein. CONCLUSIONS: The present study suggests that acute regulation of NaPi-IIc protein by PTH is involved in the inactivation of Na+-dependent Pi cotransporter activity and that phosphorylation of the transporter is involved in the rapid modification. Clinical and experimental nephrology 23 7 898 907 20190700 10.1007/s10157-019-01725-6 30895530 shiozaki_y/published_papers/32165809 Shohei Kohno Yuji Shiozaki Audrey L Keenan Shinobu Miyazaki-Anzai Makoto Miyazaki An N-terminal-truncated isoform of FAM134B (FAM134B-2) regulates starvation-induced hepatic selective ER-phagy. Autophagy is a conserved system that adapts to nutrient starvation, after which proteins and organelles are degraded to recycle amino acids in response to starvation. Recently, the ER was added to the list of targets of autophagic degradation. Autophagic degradation pathways of bulk ER and the specific proteins sorted through the ER are considered key mechanisms in maintaining ER homeostasis. Four ER-resident proteins (FAM134B, CCPG1, SEC62, and RTN3) have been identified as ER-resident cargo receptors, which contain LC3-interacting regions. In this study, we identified an N-terminal-truncated isoform of FAM134B (FAM134B-2) that contributes to starvation-induced ER-related autophagy. Hepatic FAM134B-2 but not full-length FAM134B (FAM134B-1) is expressed in a fed state. Starvation drastically induces FAM134B-2 but no other ER-resident cargo receptors through transcriptional activation by C/EBPβ. C/EBPβ overexpression increases FAM134B-2 recruitment into autophagosomes and lysosomal degradation. FAM134B-2 regulates lysosomal degradation of ER-retained secretory proteins such as ApoCIII. This study demonstrates that the C/EBPβ-FAM134B-2 axis regulates starvation-induced selective ER-phagy. Life science alliance 2 3 null null 20190600 10.26508/lsa.201900340 31101736 shiozaki_y/published_papers/32165812 Toru Fujii Yuji Shiozaki Hiroko Segawa Shiori Nishiguchi Ai Hanazaki Miwa Noguchi Ruri Kirino Sumire Sasaki Kazuya Tanifuji Megumi Koike Mizuki Yokoyama Yuki Arima Ichiro Kaneko Sawako Tatsumi Mikiko Ito Ken-Ichi Miyamoto Analysis of opossum kidney NaPi-IIc sodium-dependent phosphate transporter to understand Pi handling in human kidney. BACKGROUND: The role of Na+-dependent inorganic phosphate (Pi) transporters in the human kidney is not fully clarified. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by loss-of-function mutations in the IIc Na+-dependent Pi transporter (NPT2c/Npt2c/NaPi-IIc) gene. Another Na+-dependent type II transporter, (NPT2A/Npt2a/NaPi-IIa), is also important for renal Pi reabsorption in humans. In mice, Npt2c deletion does not lead to hypophosphatemia and rickets because Npt2a compensates for the impaired Pi reabsorption. To clarify the differences between mouse and human, we investigated the relation between NaPi-IIa and NaPi-IIc functions in opossum kidney (OK) cells. METHODS: We cloned NaPi-IIc from OK cells and created opossum NaPi-IIc (oNaPi-IIc) antibodies. We used oNaPi-IIc small interference (si)RNA and investigated the role of NaPi-IIc in Pi transport in OK cells. RESULTS: We cloned opossum kidney NaPi-IIc cDNAs encoding 622 amino acid proteins (variant1) and examined their pH- and sodium-dependency. The antibodies reacted specifically with 75-kDa and 150-kDa protein bands, and the siRNA of NaPi-IIc markedly suppressed endogenous oNaPi-IIc in OK cells. Treatment with siRNA significantly suppressed the expression of NaPi-4 (NaPi-IIa) protein and mRNA. oNaPi-IIc siRNA also suppressed Na+/H+ exchanger regulatory factor 1 expression in OK cells. CONCLUSION: These findings suggest that NaPi-IIc is important for the expression of NaPi-IIa (NaPi-4) protein in OK cells. Suppression of Npt2c may downregulate Npt2a function in HHRH patients. Clinical and experimental nephrology 23 3 313 324 20190300 10.1007/s10157-018-1653-4 30317447 shiozaki_y/published_papers/32165811 Kayo Ikuta Hiroko Segawa Ai Hanazaki Toru Fujii Ichiro Kaneko Yuji Shiozaki Sawako Tatsumi Yasuko Ishikawa Ken-Ichi Miyamoto Systemic network for dietary inorganic phosphate adaptation among three organs. Inorganic phosphate (Pi) secretion from the salivary glands and dietary Pi are key Pi sources. The regulatory mechanisms of Pi homeostasis in the salivary glands are unknown. We investigated how salivary Pi concentrations are regulated by dietary Pi in mouse models. Dietary manipulation significantly changed the levels of Npt2b protein in the salivary gland ductal cells. In addition, rapid feeding on a high-Pi diet increased the saliva Pi concentrations and led to rapid endocytosis of Npt2b in the apical membranes of the duct cells. Global Npt2b± mice exhibited increased salivary Pi concentrations and intestine-specific deletion of Npt2b after high Pi loading increased the salivary Pi concentrations. These findings indicate that Npt2b levels in the salivary glands affect the salivary Pi concentration and are regulated by dietary Pi. Intestinal Npt2b levels might also affect salivary Pi concentrations as well as renal Pi excretion. These findings suggest Pi is endogenously recycled by salivary Pi secretion, intestinal Pi absorption, and renal Pi excretion. Pflugers Archiv : European journal of physiology 471 1 123 136 20190100 10.1007/s00424-018-2242-9 30523405 shiozaki_y/published_papers/32165814 Yuji Shiozaki Kayo Okamura Shohei Kohno Audrey L Keenan Kristina Williams Xiaoyun Zhao Wallace S Chick Shinobu Miyazaki-Anzai Makoto Miyazaki The CDK9-cyclin T1 complex mediates saturated fatty acid-induced vascular calcification by inducing expression of the transcription factor CHOP. Vascular calcification (or mineralization) is a common complication of chronic kidney disease (CKD) and is closely associated with increased mortality and morbidity rates. We recently reported that activation of the activating transcription factor 4 (ATF4) pathway through the saturated fatty acid (SFA)-induced endoplasmic reticulum (ER) stress response plays a causative role in CKD-associated vascular calcification. Here, using mouse models of CKD, we 1) studied the contribution of the proapoptotic transcription factor CCAAT enhancer-binding protein homologous protein (CHOP) to CKD-dependent medial calcification, and 2) we identified an additional regulator of ER stress-mediated CHOP expression. Transgenic mice having smooth muscle cell (SMC)-specific CHOP expression developed severe vascular apoptosis and medial calcification under CKD. Screening of a protein kinase inhibitor library identified 16 compounds, including seven cyclin-dependent kinase (CDK) inhibitors, that significantly suppressed CHOP induction during ER stress. Moreover, selective CDK9 inhibitors and CRISPR/Cas9-mediated CDK9 reduction blocked SFA-mediated induction of CHOP expression, whereas inhibitors of other CDK isoforms did not. Cyclin T1 knockout inhibited SFA-mediated induction of CHOP and mineralization, whereas deletion of cyclin T2 and cyclin K promoted CHOP expression levels and mineralization. Of note, the CDK9-cyclin T1 complex directly phosphorylated and activated ATF4. These results demonstrate that the CDK9-cyclin T1 and CDK9-cyclin T2/K complexes have opposing roles in CHOP expression and CKD-induced vascular calcification. They further reveal that the CDK9-cyclin T1 complex mediates vascular calcification through CHOP induction and phosphorylation-mediated ATF4 activation. The Journal of biological chemistry 293 44 17008 17020 20181102 10.1074/jbc.RA118.004706 30209133 shiozaki_y/published_papers/32165815 Shinobu Miyazaki-Anzai Masashi Masuda Shohei Kohno Moshe Levi Yuji Shiozaki Audrey L Keenan Makoto Miyazaki Simultaneous inhibition of FXR and TGR5 exacerbates atherosclerotic formation. Simultaneous activation of bile acid receptors farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (TGR5) by INT-767 significantly reduces atherosclerotic formation. In this study, we investigated the effect of simultaneous inactivation of these bile acid receptors in atherosclerosis and which bile acid receptor mediates the anti-atherogenic effect of INT-767. To investigate the role of simultaneous inactivation of FXR and TGR5 in vivo, we generated LDL receptor knockout (LDLR) KO mice with FXR and TGR5 dual deficiency, which exhibited severe atherosclerosis and aortic inflammation through nuclear factor κΒ activation. The lipid-lowering effects of INT-767 were completely blocked by FXR single deficiency but not TGR5 single deficiency. INT-767 was able to block atherosclerotic formation and decrease levels of aortic cytokines and chemokines in LDLR KO mice under either FXR or TGR5 single deficiency. Dual deficiency of FXR and TGR5 completely blocked the anti-atherogenic and anti-inflammatory effects of INT-767 in LDLR KO mice. We demonstrated that 1) FXR and TGR5 dual deficiency exacerbated the development of atherosclerosis and 2) the anti-atherogenic effect of INT-767 requires the anti-inflammatory effect but not the lipid-lowering effect through the simultaneous activation of FXR and TGR5. Our results indicate that dual activation of FXR and TGR5 is a promising strategy for treating atherosclerosis. Journal of lipid research 59 9 1709 1713 20180900 10.1194/jlr.M087239 29976576 shiozaki_y/published_papers/32165813 Shohei Sasaki Hiroko Segawa Ai Hanazaki Ruri Kirino Toru Fujii Kayo Ikuta Miwa Noguchi Sumire Sasaki Megumi Koike Kazuya Tanifuji Yuji Shiozaki Ichiro Kaneko Sawako Tatsumi Takaaki Shimohata Yoshichika Kawai Sonoko Narisawa José Luis Millán Ken-Ichi Miyamoto A Role of Intestinal Alkaline Phosphatase 3 (Akp3) in Inorganic Phosphate Homeostasis. BACKGROUND/AIMS: Hyperphosphatemia is a serious complication of late-stage chronic kidney disease (CKD). Intestinal inorganic phosphate (Pi) handling plays an important role in Pi homeostasis in CKD. We investigated whether intestinal alkaline phosphatase 3 (Akp3), the enzyme that hydrolyzes dietary Pi compounds, is a target for the treatment of hyperphosphatemia in CKD. METHODS: We investigated Pi homeostasis in Akp3 knockout mice (Akp3-/-). We also studied the progression of renal failure in an Akp3-/- mouse adenine treated renal failure model. Plasma, fecal, and urinary Pi and Ca concentration were measured with commercially available kit, and plasma fibroblast growth factor 23, parathyroid hormone, and 1,25(OH)2D3 concentration were measured with ELISA. Brush border membrane vesicles were prepared from mouse intestine using the Ca2+ precipitation method and used for Pi transport activity and alkaline phosphatase activity. In vivo intestinal Pi absorption was measured with oral 32P administration. RESULTS: Akp3-/- mice exhibited reduced intestinal type II sodium-dependent Pi transporter (Npt2b) protein levels and Na-dependent Pi co-transport activity. In addition, plasma active vitamin D levels were significantly increased in Akp3-/- mice compared with wild-type animals. In the adenine-induced renal failure model, Akp3 gene deletion suppressed hyperphosphatemia. CONCLUSION: The present findings indicate that intestinal Akp3 deletion affects Na+-dependent Pi transport in the small intestine. In the adenine-induced renal failure model, Akp3 is predicted to be a factor contributing to suppression of the plasma Pi concentration. Kidney & blood pressure research 43 5 1409 1424 20180000 10.1159/000493379 30212831 shiozaki_y/published_papers/32165816 Masashi Masuda Shinobu Miyazaki-Anzai Audrey L Keenan Yuji Shiozaki Kayo Okamura Wallace S Chick Kristina Williams Xiaoyun Zhao Shaikh Mizanoor Rahman Yin Tintut Christopher M Adams Makoto Miyazaki Activating transcription factor-4 promotes mineralization in vascular smooth muscle cells. Emerging evidence indicates that upregulation of the ER stress-induced pro-osteogenic transcription factor ATF4 plays an important role in vascular calcification, a common complication in patients with aging, diabetes, and chronic kidney disease (CKD). In this study, we demonstrated the pathophysiological role of ATF4 in vascular calcification using global Atf4 KO, smooth muscle cell-specific (SMC-specific) Atf4 KO, and transgenic (TG) mouse models. Reduced expression of ATF4 in global ATF4-haplodeficient and SMC-specific Atf4 KO mice reduced medial and atherosclerotic calcification under normal kidney and CKD conditions. In contrast, increased expression of ATF4 in SMC-specific Atf4 TG mice caused severe medial and atherosclerotic calcification. We further demonstrated that ATF4 transcriptionally upregulates the expression of type III sodium-dependent phosphate cotransporters (PiT1 and PiT2) by interacting with C/EBPβ. These results demonstrate that the ER stress effector ATF4 plays a critical role in the pathogenesis of vascular calcification through increased phosphate uptake in vascular SMCs. JCI insight 1 18 e88646 null 20161103 10.1172/jci.insight.88646 27812542 shiozaki_y/published_papers/32165819 Sawako Tatsumi Atsumi Miyagawa Ichiro Kaneko Yuji Shiozaki Hiroko Segawa Ken-Ichi Miyamoto Regulation of renal phosphate handling: inter-organ communication in health and disease. 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. Journal of bone and mineral metabolism 34 1 1 10 20160100 10.1007/s00774-015-0705-z 26296817 shiozaki_y/published_papers/32165818 Yuji Shiozaki Hiroko Segawa Saori Ohnishi Akiko Ohi Mikiko Ito Ichiro Kaneko Shinsuke Kido Sawako Tatsumi Ken-ichi Miyamoto Relationship between sodium-dependent phosphate transporter (NaPi-IIc) function and cellular vacuole formation in opossum kidney cells. 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. The journal of medical investigation : JMI 62 3-4 209 18 20150000 10.2152/jmi.62.209 26399350 shiozaki_y/published_papers/32165817 Hiroko Segawa Yuji Shiozaki Ichiro Kaneko Ken-ichi Miyamoto The Role of Sodium-Dependent Phosphate Transporter in Phosphate Homeostasis. Inorganic phosphate (Pi) is an essential compound for several biologic functions. Pi levels outside the normal range, however, contribute to several pathological processes. Hypophosphatemia leads to bone abnormalities, such as rickets/osteomalacia. Hyperphosphatemia contributes to vascular calcification in patients with chronic kidney disease and hemodialysis patients and is independently associated with cardiac mortality.Pi homeostasis is regulated by the coordinated function of renal and intestinal sodium-dependent phosphate (NaPi) transporters with dietary Pi, parathyroid hormone, 1,25-dihydroxyvitamin D3, and fibroblast growth factor 23. The type II NaPi transporter/SLC34 family, with three members identified to date, is mainly responsible for Pi homeostasis in the body. SLC34A1 and SCL34A3 are predominantly expressed in the kidney, whereas SLC34A2 is expressed in the small intestine. The role of each SLC34 in the body was recently established by studies of gene-targeted mice. Mutation of SLC34A1 causes Fanconi syndrome and mutation of SLC34A3 causes autosomal recessive hereditary hypophosphatemic rickets with hypercalciuria. SLC34A2 is thought to be a major intestinal NaPi transporter and mutation of SLC34A2 causes pulmonary alveolar microlithiasis. A detailed understanding of Pi regulation in the body is important toward maintaining health. Journal of nutritional science and vitaminology 61 Suppl S119-21 null 20150000 10.3177/jnsv.61.S119 26598821 shiozaki_y/published_papers/32165820 Kengo Nomura Sawako Tatsumi Atsumi Miyagawa Yuji Shiozaki Shohei Sasaki Ichiro Kaneko Mikiko Ito Shinsuke Kido Hiroko Segawa Mitsue Sano Tsutomu Fukuwatari Katsumi Shibata Ken-ichi Miyamoto Hepatectomy-related hypophosphatemia: a novel phosphaturic factor in the liver-kidney axis. 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. Journal of the American Society of Nephrology : JASN 25 4 761 72 20140400 10.1681/ASN.2013060569 24262791 shiozaki_y/published_papers/32165821 Hiroko Segawa 瀬川 博子 Yuji Shiozaki 塩崎 雄治 Sakura Minoshima 蓑島 さくら Ken-ichi Miyamoto 宮本 賢一 [Updates on rickets and osteomalacia: the role of NaPi-2c/SLC34A3 and hypophosphataemic rickets]. 【くる病・骨軟化症UPDATE】NaPi-2c/SLC34A3とその遺伝子異常による疾患 Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) , an autosomal recessive disorder first identified in a large Bedouin tribe, is characterized by hypophosphatemia secondary to renal inorganic phosphate (Pi) wasting, resulting in increased serum1,25-dihydroxyvitamin D3 concentrations with associated intestinal calcium hyperabsorption, hypercalciuria, rickets, and osteomalacia. Recent studies identified several mutations in the NaPi-2c/NPT2c transporter gene (SLC34A3) as the cause of HHRH. The fact that HHRH is caused by NaPi-2c loss-of-function mutations is compatible with the HHRH phenotype and the prevailing view of renal Pi regulation. The NaPi-2c mutants in HHRH show defective processing and stability. (株)医薬ジャーナル社 Clinical calcium Clinical Calcium 0917-5857 23 10 1445 1450 20130900 24076642 shiozaki_y/published_papers/32165823 Shinsuke Kido Kengo Nomura Shohei Sasaki Yuji Shiozaki Hiroko Segawa Sawako Tatsumi [Information about phosphorus additives and nutritional counseling]. Hyperphosphatemia is a common disorder in patients with chronic kidney disease (CKD) , and may result in hyperparathyroidism and renal osteodystrophy. Hyperphosphatemia also may contribute to deterioration vascular calcification and increase mortality. Hence, correction and prevention of hyperphosphatemia is a main component of the management of CKD. This goal is usually approached both by administering phosphorus binders and by restricting dietary phosphorus (P) intake. Dietary intake of phosphorus (P) is derived largely from foods with high protein content or food additives and is an important determinant of P balance in patient with CKD. Food additives (PO4) can dramatically increase the amount of P consumed in the daily diet, especially because P is more readily absorbed in its inorganic form. In addition, information about the P content and type in prepared foods is often unavailable or misleading. Therefore, during dietary counseling of patients with CKD, we recommended that they consider both the absolute dietary P content and the P-to-protein ratio of foods and meals including food additives. Clinical calcium 0917-5857 22 10 1583 91 20121000 23023640 shiozaki_y/published_papers/32165824 Sakiko Haito-Sugino Mikiko Ito Akiko Ohi Yuji Shiozaki Natsumi Kangawa Takashi Nishiyama Fumito Aranami Shohei Sasaki Ayaka Mori Shinsuke Kido Sawako Tatsumi Hiroko Segawa Ken-Ichi Miyamoto Processing and stability of type IIc sodium-dependent phosphate cotransporter mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria. 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. American journal of physiology. Cell physiology 302 9 C1316-30 null 20120501 10.1152/ajpcell.00314.2011 22159077 shiozaki_y/published_papers/32165822 Shinsuke Kido Marina Fujihara Kengo Nomura Shohei Sasaki Yuji Shiozaki Hiroko Segawa Sawako Tatsumi Ken-ichi Miyamoto [Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium]. Phosphaturia has been documented following cadmium (Cd) exposure in both humans and experimental animals. Fibroblast growth factor 23 (FGF23) serves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the present study, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. Following Cd injection into C57BL/6J mice, plasma FGF23 concentration significantly increased. The urinary Pi excretion level was significantly higher in the Cd-injected C57BL/6J mice than in the control group. Plasma Pi concentration decreased only slightly in the Cd-injected mice compared with the control group. No changes were observed in the concentration of the plasma parathyroid hormone and 1,25-dihydroxy vitamin D(3) in both groups of mice. We observed a decrease in phosphate transport activity and also a decrease in the expression level of renal phosphate transporter Npt2c, but not that of Npt2a. Furthermore, we examined the effect of Cd on Npt2c in Npt2a-knockout (KO) mice, which expresses Npt2c as a major NaPi cotransporter. Injecting Cd to Npt2aKO mice induced a significant increase in plasma FGF23 concentration and urinary Pi excretion level. Furthermore, we observed decreases in phosphate transport activity and renal Npt2c expression level in the Cd-injected Npt2a KO mice. The present study suggests that hypophosphatemia induced by Cd may be closely associated with FGF23. Nihon eiseigaku zasshi. Japanese journal of hygiene 1882-6482 67 4 464 71 20120000 23095356 shiozaki_y/misc/52766190 小池 萌 塩﨑 雄治 瀬川 博子 尿細管リン酸イオン再吸収機構の最新知見—Progress in understanding tubular phosphate handling in the kidney—特集 リン代謝研究の最新動向と臨床的意義 東京 : 医歯薬出版 医学のあゆみ 0039-2359 294 8 558 563 20250823 1520305411869312128 shiozaki_y/misc/48889534 三浦美月 三浦美月 三浦美月 佐々木すみれ 塩崎雄治 小池萌 宇賀穂 東彩生 長谷川智香 網塚憲生 宮本賢一 宮本賢一 瀬川博子 Tmem174はリン酸トランスポーターを調節し高リン血症を予防する新規リン代謝調節分子である 日本骨代謝学会学術集会プログラム抄録集(CD-ROM) 1349-0761 41st null null 20230000 shiozaki_y/misc/46713802 小池萌 塩崎雄治 瀬川博子 Maintenance of inorganic phosphate homeostasis CKD-MBDの新しい潮流 CKD-MBDの病態 無機リン酸の恒常性維持 腎と透析 0385-2156 95 3 null null 20230000 shiozaki_y/misc/49218552 佐々木すみれ 佐々木すみれ 塩崎雄治 小池萌 谷藤和也 宇賀穂 WIRIYASERMKUL Pattama 長谷川智香 網塚憲生 宮本賢一 宮本賢一 永森收志 金井好克 瀬川博子 Tmem174はリン酸トランスポーターを調節し高リン血症を予防する 日本生化学会大会(Web) 95th null null 20220000 shiozaki_y/misc/40943738 瀬川博子 小池萌 塩崎雄治 宮本賢一 宮本賢一 Mineral Nutrition to Regulate Anti-Aging Factors-phosphorus- 食品の機能性と栄養・代謝物シグナル 4.抗老化因子を制御するミネラル栄養学-リン代謝恒常性制御の重要性 実験医学 0288-5514 40 7 null null 20220000 shiozaki_y/misc/40943743 川原滉太 小池萌 佐々木すみれ 谷藤和也 塩崎雄治 金子一郎 瀬川博子 ライフステージに着目した生体内リン代謝の性差検討 日本栄養・食糧学会大会講演要旨集 75th null null 20210000 shiozaki_y/misc/40943740 川原滉太 小池萌 佐々木すみれ 谷藤和也 塩崎雄治 金子一郎 瀬川博子 ライフステージに着目した生体内リン代謝の性差検討 栄養学雑誌 0021-5147 79 5 Supplement null null 20210000 shiozaki_y/misc/32166298 SEGAWA Hiroko SHIOZAKI Yuji KANEKO Ichiro MINAMOTO Ken-Ichi Phosphate balance in the body and epithelial phosphate transporters 体内のリン酸バランスと上皮リン酸トランスポーター Journal of Physiological Sciences (Web) 1880-6546 69 Supplement 1 null null 20190000 shiozaki_y/misc/32166300 瀬川博子 藤井公 西口詩織 塩崎雄治 宮本賢一 リン酸トランスポーターSLC34の生理学的役割 トランスポーター研究会年会抄録集 11th null null 20160000 shiozaki_y/misc/32165901 塩崎 雄治 宮本 賢一 【慢性腎臓病と老化-Phosphate connection】リンの栄養学 食物中のリンと食品添加物 (株)日本メディカルセンター 腎と骨代謝 2433-2496 28 1 69 78 20150100 shiozaki_y/misc/32165903 塩崎 雄治 宮本 賢一 【医学・医療のいまがわかるキーワード2014】腎臓内科 FGF23(骨分泌性線維芽細胞増殖因子) 医歯薬出版(株) 医学のあゆみ 0039-2359 249 5 427 427 20140500 shiozaki_y/misc/32165902 塩崎 雄治 瀬川 博子 大西 沙織 大井 彰子 杉野 紗貴子 簑島 さくら 伊藤 美紀子 木戸 慎介 辰巳 佐和子 宮本 賢一 近位尿細管上皮細胞におけるNa+依存性無機リン酸輸送担体Npt2cの発現調節とVacuole形成 (公社)日本生化学会 日本生化学会大会プログラム・講演要旨集 86 2T11p 09 20130900 shiozaki_y/misc/32165906 瀬川 博子 大西 沙織 塩崎 雄治 佐々木 祥平 宮本 賢一 【尿細管トランスポーターの機能制御と疾患治療-トピックス】リン輸送と疾患 (株)日本メディカルセンター 腎と骨代謝 2433-2496 26 3 187 192 20130700 shiozaki_y/misc/32165905 野村 憲吾 辰巳 佐和子 宮川 淳美 岡 奈都紀 塩崎 雄治 木戸 慎介 瀬川 博子 佐野 光枝 福渡 努 柴田 克己 宮本 賢一 肝臓切除患者における低リン血症発症機構の解明 (公社)日本栄養・食糧学会 日本栄養・食糧学会大会講演要旨集 67 173 173 20130400 shiozaki_y/misc/32165904 木戸 慎介 越智 美佐子 藤原 真理奈 向井 朋 塩崎 雄治 瀬川 博子 辰巳 佐和子 宮本 賢一 慢性腎臓病に併存する骨ミネラル代謝障害(CKD-MBD)の発症並びに進展におけるFGF23の関与 (公社)日本栄養・食糧学会 日本栄養・食糧学会大会講演要旨集 67 190 190 20130400 shiozaki_y/misc/32166301 野村憲吾 塩崎雄治 宮本賢一 Basic nephrology A.生理 1.リン調節機構の分子メカニズム Annual Review 腎臓 2013 null null 20130000 shiozaki_y/misc/32166299 野村憲吾 辰巳佐和子 宮川淳美 塩崎雄治 瀬川博子 宮本賢一 肝臓切除による無機リン酸恒常性破綻機構について 日本分子生物学会年会プログラム・要旨集(Web) 36th null null 20130000 shiozaki_y/misc/32165908 木戸 慎介 野村 憲吾 佐々木 祥平 塩崎 雄治 瀬川 博子 辰巳 佐和子 【栄養とリン∼新しい展開と課題∼】リン添加物に関する情報と栄養指導 (株)医薬ジャーナル社 Clinical Calcium 0917-5857 22 10 1583 1591 20120900 shiozaki_y/misc/32165907 木戸 慎介 藤原 真理奈 野村 憲吾 佐々木 祥平 塩崎 雄治 瀬川 博子 辰巳 佐和子 宮本 賢一 【カドミウム研究の現状と今後の展望-疫学研究から分子機構まで】カドミウム曝露によるリン代謝異常 FGF23産生亢進機序の検討 カドミウム曝露はマウスの骨におけるFGF23産生を増加させるが，これはFGF23遺伝子の転写誘導ではなく，FGF23の翻訳後修飾に関わるO型糖鎖修飾酵素GalNAc-T3の誘導によるプロセシングの抑制に起因したものである可能性を明らかにした．また，カドミウムによるリン利尿の発症機序として，カドミウム曝露により増加したFGF23が標的臓器である腎臓に作用し，近位尿細管刷子縁膜に発現するリン輸送担体の抑制を介してリン利尿を引き起こす可能性が考えられる．「カドミウム曝露による腎障害・骨障害の発症とFGF23」「カドミウム曝露によるリン代謝障害とその分子機序」「カドミウム曝露によるFGF23産生亢進機序」について述べた． (一社)日本衛生学会 日本衛生学雑誌 1882-6482 67 4 464 471 20120900 shiozaki_y/misc/32166024 塩崎雄治 木戸慎介 辰巳佐和子 伊藤美紀子 杉野紗貴子 大井彰子 瀬川博子 宮本賢一 近位尿細管上皮細胞における細胞密度を介したNa⁺依存性無機リン酸輸送担体Npt2aおよびNpt2cの発現調節機構 日本分子生物学会年会プログラム・要旨集(Web) 35th null null 20120000 shiozaki_y/misc/32165910 野村 憲吾 辰巳 佐和子 山口 誠一 塩崎 雄治 菅生 陵馬 木戸 慎介 瀬川 博子 宮本 賢一 肝臓切除による低リン血症発症メカニズムの解明 (株)日本メディカルセンター 腎と骨代謝 2433-2496 24 4 318 318 20111000 shiozaki_y/misc/32165911 塩崎 雄治 杉野 さきこ 大井 彰子 辰巳 佐和子 伊藤 美紀子 宮本 賢一 高カルシウム尿を伴う遺伝性低リン血症性クル病の原因遺伝子リン酸トランスポーターNPT2cの変異体解析 (一社)日本腎臓学会 日本腎臓学会誌 1884-0728 53 3 366 366 20110500 shiozaki_y/misc/32165909 辰巳 佐和子 菊井 聡子 野村 憲吾 斎藤 友紀子 塩崎 雄治 山口 誠一 木戸 慎介 瀬川 博子 宮本 賢一 リン代謝におけるカルシウム受容体の役割 (公社)日本栄養・食糧学会 日本栄養・食糧学会大会講演要旨集 65 186 186 20110400 shiozaki_y/misc/32165912 杉野 紗貴子 塩崎 雄治 辰己 佐和子 瀬川 博子 宮本 賢一 キーワード解説 ナトリウム/リン共輸送担体 (公社)日本薬理学会 日本薬理学雑誌 1347-8397 137 1 51 52 20110100 shiozaki_y/misc/32165913 山口 誠一 辰巳 佐和子 釜谷 達哉 塩崎 雄治 野村 憲吾 齋藤 友紀子 木戸 慎介 宮本 賢一 リン代謝における骨細胞の役割 (株)日本メディカルセンター 腎と骨代謝 2433-2496 23 4 343 343 20101000 shiozaki_y/misc/32165915 齋藤 友紀子 辰巳 佐和子 野村 憲吾 菊井 聡子 山口 誠一 塩崎 雄治 金子 一郎 瀬川 博子 木戸 慎介 宮本 賢一 リン酸輸送担体遺伝子欠損マウスの病態解析 (公社)日本栄養・食糧学会 日本栄養・食糧学会大会講演要旨集 64 104 104 20100500 shiozaki_y/misc/32165914 野村 憲吾 辰巳 佐和子 菊井 聡子 齋藤 友紀子 塩崎 雄治 山口 誠一 木戸 慎介 宮本 賢一 新規リン利尿因子の探索 (公社)日本栄養・食糧学会 日本栄養・食糧学会大会講演要旨集 64 105 105 20100500 shiozaki_y/misc/32165916 菊井 聡子 辰巳 佐和子 野村 憲吾 齋藤 友紀子 塩崎 雄治 山口 誠一 木戸 慎介 宮本 賢一 シナカルセト塩酸塩によるリン管理 (一社)日本病態栄養学会 日本病態栄養学会誌 1345-8167 12 5 181 181 20091200 shiozaki_y/books_etc/32166464 Yuji Shiozaki Audrey L. Keenan Makoto Miyazaki Lipid signaling and metabolism Academic Press, an imprint of Elsevier 20200000 10.1016/C2018-0-05568-1 shiozaki_y/books_etc/32166974 塩崎雄治 宮本賢一 臨床栄養実践ガイド 中外医学社 20140800 shiozaki_y/books_etc/32166750 塩﨑雄治 野村憲吾 宮本賢一 CKD-MBDハンドブック 2nd Edition 日本メディカルセンター 20130600