Tokushima University / Educator and Researcher Directory --- Hasegawa, Kazuhiro

Personal Web Page

https://researchmap.jp/read0137466 (researchmap)

Field of Study

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○	Genome Science

Subject of Study

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○	tubulo-glomerular interplay (Sirtui1 and NMN, Voclosporin-induced nephrotoxicity, mitoribosome, proximal tubular metabolism, diabetic nephropathy)

Book / Paper

(See https://researchmap.jp/read0137466 (researchmap) for Published Book / Papers / Presentations.)

Academic Paper (Judged Full Paper):

1.	Kazuhiro Hasegawa, Yusuke Sakamaki, Masanori Tamaki and Shu Wakino : Voclosporin Overdose-Induced Peroxisomal Structural Changes and AKI Are Prevented By Renal Indole Detoxifier, INMT., Journal of the American Society of Nephrology, 2025. (Link to Publication Site) ● Publication site (DOI): 10.1681/ASN.0000000751 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 40397512 ● Search Scopus @ Elsevier (PMID): 40397512 ● Search Scopus @ Elsevier (DOI): 10.1681/ASN.0000000751 (DOI: 10.1681/ASN.0000000751, PubMed: 40397512)
2.	Hidenori Urai, Tatsuhiko Azegami, Motoaki Komatsu, Rina Takahashi, Yoshiaki Kubota, Kazuhiro Hasegawa, Hirofumi Tokuyama, Shu Wakino, Kaori Hayashi, Takeshi Kanda and Hiroshi Itoh : Ghrelin Promotes Lipid Uptake into White Adipose Tissue via Endothelial Growth Hormone Secretagogue-Receptor in Mice, Nutrients, 17, 1, 2024. (Summary) Background/Objectives: Endothelial peroxisome proliferator-activated receptor gamma (PPARγ) regulates adipose tissue by facilitating lipid uptake into white adipocytes, but the role of endothelial lipid transport in systemic energy balance remains unclear. Ghrelin conveys nutritional information through the central nervous system and increases adiposity, while deficiency in its receptor, growth hormone secretagogue-receptor (GHSR), suppresses adiposity on a high-fat diet. This study aims to examine the effect of ghrelin/GHSR signaling in the endothelium on lipid metabolism. Methods: We compared the effects of ghrelin on adiposity and lipid uptake into adipocytes in wild-type and GHSR-null mice. Transgenic mice expressing GHSR selectively in endothelial cells were also generated and compared with global GHSR-null and wild-type mice. The impact of ghrelin on lipid uptake-related genes was assessed in cultured endothelial cells. Results: Ghrelin increased adiposity and triglyceride clearance in wild-type but not in GHSR-null mice. GHSR-null mice showed higher serum triglyceride after olive oil gavage and lower white adipose tissue (WAT) weight on a high-fat diet, suggesting impaired lipid uptake. Restoring GHSR expression in endothelial cells increased lipoprotein lipase activity, lipid uptake into WAT, and WAT weight. Ghrelin enhanced free fatty acid uptake and the expression of lipid uptake genes in cultured endothelial cells, whereas these effects were absent in GHSR-null mice-derived endothelial cells. Knockdown of PPARγ revealed that ghrelin/GHSR signaling in endothelial cells promoted lipid uptake via endothelial PPARγ. Conclusions: Endothelial GHSR is key for regulating lipid metabolism via PPARγ in response to ghrelin and for the role of endothelium in regulating white adipocyte metabolism. Targeting endothelial ghrelin signaling may be a promising therapeutic approach for managing excessive adiposity and associated metabolic disorders. (Keyword) endothelial cells / ghrelin / growth hormone secretagogue-receptor / obesity / triglyceride (Link to Publication Site) ● Publication site (DOI): 10.3390/nu17010146 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 39796581 ● Summary page in Scopus @ Elsevier: 2-s2.0-85214514845 (DOI: 10.3390/nu17010146, PubMed: 39796581, Elsevier: Scopus)
3.	Masanori Tamaki, Taizo Inagaki, Masanori Minato, Eriko Shibata, Rika Nishioka, Satoshi Nishioka, Yukiko Matsubara, Masamitsu Sasaki, Motoyuki Tamaki, Masaharu Tamaki, Kazuhiro Hasegawa, Kojiro Nagai and Shu Wakino : Roxadustat for Treating Anemia in Patients with Advanced Chronic Kidney Disease Not Undergoing Dialysis: A Retrospective Study, Internal Medicine, 64, 9, 1303-1314, 2024. (Summary) Objective Roxadustat, a hypoxia-inducible factor-prolyl hydroxylase inhibitor, increases the hemoglobin (Hb) levels in patients with chronic kidney disease (CKD). To date, limited clinical studies have focused on the excessive increase in the Hb levels in the early weeks after switching from erythropoiesis-stimulating agents (ESA) to roxadustat in adult non-dialysis patients. We conducted a retrospective study to examine whether early overshoot frequently occurs after switching to roxadustat. Methods This 8-week retrospective pilot study examined patients with anemic, non-dialyzed CKD who switched from ESA (darbepoetin or epoetin beta pegol) to roxadustat or continued ESA. The Hb levels >12.5 g/dL after starting our observation was defined as Hb overshoot. Patients: Twenty-three patients who switched to roxadustat (roxadustat group) and 63 who continued ESA (ESA group) were included. Results The baseline median estimated glomerular filtration rate and mean Hb levels were 15.7 mL/min/1.73 m² and 10.77 g/dL in roxadustat group and 15.2 mL/min/1.73 m² and 10.64 g/dL in ESA group, respectively. Eight patients (34.8%) in the roxadustat group and two patients (3.2%) in the ESA group had Hb overshoot within the 8-week visit [odds ratio: 20.2 (95% confidence interval 3.13-130.0, p<0.01) in the background adjusted model]. Among the patients with Hb overshoot in the roxadustat group, the Hb levels were maintained close to baseline 4 weeks after roxadustat discontinuation. A younger age and higher baseline Hb and Hct levels were risk factors for Hb overshoot. Conclusion Hb overshoot was frequently observed in patients switched to roxadustat. Clinicians should be aware of Hb overshoot and emphasize the importance of early Hb level checks. (Keyword) chronic kidney disease / real-world evidence / renal anemia / roxadustat (Link to Publication Site) ● Publication site (DOI): 10.2169/internalmedicine.3773-24 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 39370259 ● Summary page in Scopus @ Elsevier: 2-s2.0-105004022755 (DOI: 10.2169/internalmedicine.3773-24, PubMed: 39370259, Elsevier: Scopus)
4.	Kazuhiro Hasegawa, Masanori Tamaki, Yusuke Sakamaki and Shu Wakino : Deficiency Causes Mitoribosome Excess in Diabetic Nephropathy Mediated by Transcriptional Repressor HIC1., International Journal of Molecular Sciences, 25, 12, 2024. (Summary) overexpression preserved mitoribosomal function, suggesting its protective role in DN. (Keyword) Animals / Male / Mice / Diabetic Nephropathies / Kidney Tubules, Proximal / Mice, Inbred C57BL / Mice, Knockout / Mitochondria / Nicotinamide-Nucleotide Adenylyltransferase (Tokushima University Institutional Repository) ● Metadata: 2012210 (Link to Publication Site) ● Publication site (DOI): 10.3390/ijms25126384 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38928090 ● Search Scopus @ Elsevier (PMID): 38928090 ● Search Scopus @ Elsevier (DOI): 10.3390/ijms25126384 (Tokushima University Institutional Repository: 2012210, DOI: 10.3390/ijms25126384, PubMed: 38928090)
5.	Kazuhiro Hasegawa, Masanori Tamaki, Eriko Shibata, Taizo Inagaki, Masanori Minato, Sumiyo Yamaguchi, Ikuko Shimizu, Shinji Miyakami, Miho Tada and Shu Wakino : Ability of NAD and Sirt1 to epigenetically suppress albuminuria., Clinical and Experimental Nephrology, 28, 7, 599-607, 2024. (Summary) The time for diabetic nephropathy (DN) to progress from mild to severe is long. Thus, methods to continuously repress DN are required to exert long-lasting effects mediated through epigenetic regulation. In this study, we demonstrated the ability of nicotinamide adenine dinucleotide (NAD) and its metabolites to reduce albuminuria through Sirt1- or Nampt-dependent epigenetic regulation. We previously reported that proximal tubular Sirt1 was lowered before glomerular Sirt1. Repressed glomerular Sirt1 was found to epigenetically elevate Claudin-1. In addition, we reported that proximal tubular Nampt deficiency epigenetically augmented TIMP-1 levels in Sirt6-mediated pathways, leading to type-IV collagen deposition and diabetic fibrosis. Altogether, we propose that the Sirt1/Claudin-1 axis may be crucial in the onset of albuminuria at the early stages of DN and that the Nampt/Sirt6/TIMP-1 axis promotes diabetic fibrosis in the middle to late stages of DN. Finally, administration of NMN, an NAD precursor, epigenetically potentiates the regression of the onset of DN to maintain Sirt1 and repress Claudin-1 in podocytes, suggesting the potential use of NAD metabolites as epigenetic medications for DN. (Keyword) Animals / Humans / Albuminuria / Claudin-1 / Cytokines / Diabetic Nephropathies / Epigenesis, Genetic / Fibrosis / Kidney Tubules, Proximal / Mice, Inbred C57BL / Mice, Knockout / NAD / Nicotinamide Mononucleotide / Nicotinamide Phosphoribosyltransferase / Podocytes / Sirtuin 1 / Sirtuins / Tissue Inhibitor of Metalloproteinase-1 (Tokushima University Institutional Repository) ● Metadata: 2012209 (Link to Publication Site) ● Publication site (DOI): 10.1007/s10157-024-02502-w (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 38587753 ● Summary page in Scopus @ Elsevier: 2-s2.0-85189697626 ● Summary page in Scopus @ Elsevier: 2-s2.0-85196749614 (Tokushima University Institutional Repository: 2012209, DOI: 10.1007/s10157-024-02502-w, PubMed: 38587753, Elsevier: Scopus, Elsevier: Scopus)
6.	Kazuhiro Hasegawa, Yusuke Sakamaki, Masanori Tamaki and Shu Wakino : PCK1 Protects against Mitoribosomal Defects in Diabetic Nephropathy in Mouse Models., Journal of the American Society of Nephrology, 34, 8, 1343-1365, 2023. (Summary) PCK1 preserves mitoribosomal function and may play a novel protective role in DN. (Keyword) Mice / Animals / Diabetic Nephropathies / Diabetes Mellitus, Experimental / Collagen Type IV / Albuminuria / Diabetes Mellitus, Type 2 / Phosphoenolpyruvate / Phosphoenolpyruvate Carboxykinase (GTP) / Sodium-Glucose Transporter 2 Inhibitors / Disease Models, Animal / Mice, Transgenic / Fibrosis / Mice, Knockout / Glucose (Link to Publication Site) ● Publication site (DOI): 10.1681/ASN.0000000000000156 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 37199399 ● Search Scopus @ Elsevier (PMID): 37199399 ● Search Scopus @ Elsevier (DOI): 10.1681/ASN.0000000000000156 (DOI: 10.1681/ASN.0000000000000156, PubMed: 37199399)
7.	Itaru Yasuda, Kazuhiro Hasegawa, Yusuke Sakamaki, Hirokazu Muraoka, Takahisa Kawaguchi, Ei Kusahana, Takashi Ono, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino and Hiroshi Itoh : Pre-emptive short-term nicotinamide mononucleotide treatment in a mouse model of diabetic nephropathy, Journal of the American Society of Nephrology, 32, 6, 1355-1370, 2021. (Summary) The activation of NAD⁺-dependent deacetylase, Sirt1, by the administration of nicotinamide mononucleotide (NMN) ameliorates various aging-related diseases. Diabetic db/db mice were treated with NMN transiently for 2 weeks and observed for effects on diabetic nephropathy (DN). At 14 weeks after the treatment period, NMN attenuated the increases in urinary albumin excretion in db/db mice without ameliorating hemoglobin A1c levels. Short-term NMN treatment mitigated mesangium expansion and foot process effacement, while ameliorating decreased Sirt1 expression and increased claudin-1 expression in the kidneys of db/db mice. This treatment also improved the decrease in the expression of H3K9me2 and DNMT1. Short-term NMN treatment also increased kidney concentrations of NAD⁺ and the expression of Sirt1 and nicotinamide phosphoribosyltransferase (Nampt), and it maintained nicotinamide mononucleotide adenyltransferase1 (Nmnat1) expression in the kidneys. In addition, survival rates improved after NMN treatment. Short-term NMN treatment in early-stage DN has remote renal protective effects through the upregulation of Sirt1 and activation of the NAD⁺ salvage pathway, both of which indicate NMN legacy effects on DN. (Keyword) Albuminuria / Animals / Claudin-1 / Cytokines / DNA (Cytosine-5-)-Methyltransferase 1 / Diabetic Nephropathies / Disease Models, Animal / Dose-Response Relationship, Drug / Epigenesis, Genetic / Glomerular Mesangium / Glycated Hemoglobin / Histones / Male / Mice / Mice, Knockout / NAD / Nicotinamide Mononucleotide / Nicotinamide Phosphoribosyltransferase / Nicotinamide-Nucleotide Adenylyltransferase / Podocytes / Sirtuin 1 / Survival Rate / Time Factors (Link to Publication Site) ● Publication site (DOI): 10.1681/ASN.2020081188 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33795425 ● Summary page in Scopus @ Elsevier: 2-s2.0-85107319498 (DOI: 10.1681/ASN.2020081188, PubMed: 33795425, Elsevier: Scopus)
8.	Takahisa Kawaguchi, Kazuhiro Hasegawa, Itaru Yasuda, Hirokazu Muraoka, Hiroyuki Umino, Hirobumi Tokuyama, Akinori Hashiguchi, Shu Wakino and Hiroshi Itoh : Diabetic condition induces hypertrophy and vacuolization in glomerular parietal epithelial cells, Scientific Reports, 11, 1, 1515, 2021. (Summary) Diabetic nephropathy (DN) is accompanied by characteristic changes in the glomerulus, but little is known about the effect of diabetes on parietal epithelial cells (PECs). In this study, a descriptive analysis of PECs was undertaken in diabetic db/db mice and in diabetic patients. PEC hypertrophy was significantly more prominent in diabetic mice than in nondiabetic mice, and this was evident even at the early stage. Additionally, the number of vacuoles in PECs was markedly increased in diabetic mice, suggesting the presence of cellular injury in PECs in DN. Although rare, binuclear cells were observed in mice with early diabetes. In cultured PECs, a high glucose condition, compared with normal glucose condition, induced cellular hypertrophy and apoptosis. Flow cytometry showed that some PECs in the G0 phase reentered the cell cycle but got arrested in the S phase. Finally, in human diabetic subjects, hypertrophy and vacuolization were observed in the PECs. Our data showed that PECs undergo substantial changes in DN and may participate in rearrangement for differentiation into podocytes. (Keyword) Adult / Aged / Animals / Bowman Capsule / Cell Differentiation / Cells, Cultured / Diabetes Mellitus / Diabetes Mellitus, Experimental / Diabetic Nephropathies / Disease Models, Animal / Epithelial Cells / Female / Humans / Hypertrophy / Kidney Glomerulus / Male / Mice / Mice, Obese / Middle Aged / Podocytes (Link to Publication Site) ● Publication site (DOI): 10.1038/s41598-021-81027-8 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33452384 ● Summary page in Scopus @ Elsevier: 2-s2.0-85099472433 (DOI: 10.1038/s41598-021-81027-8, PubMed: 33452384, Elsevier: Scopus)

Review, Commentary:

1.	Masanori Tamaki, Kazuhiro Hasegawa and Shu Wakino : 特集内科医に知ってもらいたいシン·腎臓診療 [Chapter 4] 腎臓内科での使い方から学ぶ! 最近よく見るあの薬 RAS阻害薬に続け! 慢性腎臓病におけるARNI·MRAの新展開, Internal Medicine, 136, 1, 83-85, Jul. 2025. (Link to Publication Site) ● Publication site (DOI): 10.15106/j_naika136_83 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390304560096488064 ● Search Scopus @ Elsevier (DOI): 10.15106/j_naika136_83 (DOI: 10.15106/j_naika136_83, CiNii: 1390304560096488064)
2.	Kazuhiro Hasegawa, Masanori Tamaki and Shu Wakino : 特集腎臓とエイジング/アンチエイジング各論腎臓の老化のメカニズムサーチュイン遺伝子と腎老化のVORTICE(ヴォルティーチェ), 腎と透析, 98, 6, 811-816, Jun. 2025. (Link to Publication Site) ● Publication site (DOI): 10.24479/kd.0000001925 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390023239819007872 ● Search Scopus @ Elsevier (DOI): 10.24479/kd.0000001925 (DOI: 10.24479/kd.0000001925, CiNii: 1390023239819007872)
3.	Shu Wakino, Kazuhiro Hasegawa, Masanori Tamaki, Masanori Minato and Taizo Inagaki : Kidney-Gut Axis in Chronic Kidney Disease: Therapeutic Perspectives from Microbiota Modulation and Nutrition, Nutrients, 17, 12, Jun. 2025. (Summary) Chronic kidney disease (CKD) has a high prevalence worldwide, with an increasing incidence. One of the mechanisms of CKD progression involves a disordered inter-organ relationship between the kidneys and the intestine, known as the kidney-gut axis. In CKD, two pathological gut conditions-disturbed gut microbiota composition called uremic dysbiosis and leaky gut-contribute to the progression of CKD. Dysbiosis is associated with the increased production of gut-derived uremic toxins, leaky gut, and chronic systemic inflammation, leading to worsening uremia, which in turn aggravates the gut condition. This vicious cycle should be a target of the therapeutic strategy against CKD. The modulation of uremic dysbiosis, including prebiotics, probiotics, and synbiotics, has been a typical treatment approach, although clinical evidence for their efficacy has been insufficient. Some non-antibiotic drugs have an impact on human gut bacteria that are believed to play a role in their clinical efficacy on kidney function. Nutrition therapies, including a low-protein diet, dietary fiber, a Mediterranean diet, and whole grains, positively influence gut microbiota composition and have been linked to a decreased risk of CKD. Novel strategies are currently being explored, involving the use of postbiotics, microbiome sequencing techniques, and fecal microbiota transplantation, although clinical application remains to be tested. Human trials investigating the above-mentioned interventions remain inconclusive due to several limitations, including dietary variability and genetic factors. Future research should focus on the development of more effective probiotics, prebiotics, and microbial metabolism-modifying drugs, not only for CKD but for other systemic diseases as well. (Keyword) chronic kidney disease / diet / intervention / kidney-gut axis / microbiota (Link to Publication Site) ● Publication site (DOI): 10.3390/nu17121961 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 40573072 ● Summary page in Scopus @ Elsevier: 2-s2.0-105008907867 (DOI: 10.3390/nu17121961, PubMed: 40573072, Elsevier: Scopus)
4.	Kazuhiro Hasegawa and Shu Wakino : 特集今この研究が面白い! 第10章腎臓 [尿細管代謝]尿細管エネルギー代謝の全貌, Internal Medicine, 134, 3, 760-765, Sep. 2024. (Link to Publication Site) ● Publication site (DOI): 10.15106/j_naika134_760 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390019756116549632 ● Search Scopus @ Elsevier (DOI): 10.15106/j_naika134_760 (DOI: 10.15106/j_naika134_760, CiNii: 1390019756116549632)
5.	Kazuhiro Hasegawa, Masanori Tamaki, Eriko Shibata, Masanori Minato, Taizo Inagaki, 清水郁子, 山口純代, 宮上慎司, 多田美穂 and Shu Wakino : 特集糖尿病性腎症研究の最前線糖尿病性腎症の発症機序糖尿病性腎症におけるミトコンドリアの役割, Kidney and Dialysis, 96, 2, 159-164, Feb. 2024. (Link to Publication Site) ● Publication site (DOI): 10.24479/kd.0000001187 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390299528381041664 ● Search Scopus @ Elsevier (DOI): 10.24479/kd.0000001187 (DOI: 10.24479/kd.0000001187, CiNii: 1390299528381041664)
6.	Shu Wakino, Kazuhiro Hasegawa, Masanori Tamaki and Eriko Shibata : 特集血液透析患者の血圧を再考する 5.透析患者の至適血圧-腹膜透析も含む, The Japanese Journal of Clinical Dialysis, 40, 2, 155-163, Feb. 2024. (Link to Publication Site) ● Publication site (DOI): 10.19020/cd.0000002887 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390862168254226944 ● Search Scopus @ Elsevier (DOI): 10.19020/cd.0000002887 (DOI: 10.19020/cd.0000002887, CiNii: 1390862168254226944)
7.	Shu Wakino, Kazuhiro Hasegawa and Masanori Tamaki : 近位尿細管から見た糖尿病性腎臓病と肥満関連腎症, Cardioangiology, 93, 2, 182-189, Feb. 2023. (Keyword) proximal tabular cell / diabetic kidney disease / obesity / SGLT2 / Sirtuin (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520013962704009344 (CiNii: 1520013962704009344)
8.	Masanori Tamaki, Kazuhiro Hasegawa and Shu Wakino : 【急性腎障害(AKI)】AKIの病態とその対応手術とAKI, Kidney and Dialysis, 94, 1, 83-86, Jan. 2023. (Link to Publication Site) ● Publication site (DOI): 10.24479/kd.0000000586 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390016195131521024 ● Search Scopus @ Elsevier (DOI): 10.24479/kd.0000000586 (DOI: 10.24479/kd.0000000586, CiNii: 1390016195131521024)
9.	Kazuhiro Hasegawa and Shu Wakino : 【ポドサイトパチー】糖尿病性腎症におけるポドサイト傷害の見える化へ迫る最新論文, Nephrology, 15, 6, 659-664, Jun. 2022. (Keyword) podocytopathy / podocyte injury / DKD (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520011108762623872 (CiNii: 1520011108762623872)
10.	Kazuhiro Hasegawa, Masanori Tamaki, 坂巻裕介 and Shu Wakino : ミトコンドリアとSIRT1/NMNと腎臓病, Nephrology, 15, 5, 551-557, May 2022. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520292395539278336 (CiNii: 1520292395539278336)

Proceeding of International Conference:

1.	Masanori Tamaki, Tamaki Masaharu, Kazuhiro Hasegawa, Kojiro Nagai and Shu Wakino : Roxadustat for treating anemia in patients with advanced chronic kidney disease not undergoing dialysis: a pilot study, Kidney Health In Aging and Aged Societies: JSN/ERA Symposium Collaboration with JSDT, Sep. 2024.
2.	Takeshi Kanda, Koichi Hayashi, Shu Wakino, Koichiro Homma, Kyoko Yoshioka, Kazuhiro Hasegawa, Naoki Sugano, Satoru Tatematsu, Ichiro Takamatsu, Takayuki Mitsuhashi and Takao Saruta : Role of Rho-kinase and p27 in angiotensin II-induced vascular injury, Hypertension, 45, 4 SUPPL., 724-729, Feb. 2005. (Summary) Angiotensin II enhances the development of atherosclerotic lesion in which cellular proliferation and/or migration are critical steps. Although cyclin-dependent kinase inhibitor, p27, and Rho/Rho-kinase pathway have recently been implicated as factors regulating these events cooperatively, their role in vivo has not been fully elucidated. We evaluated the contribution of p27 and Rho-kinase to angiotensin II-induced vascular injury using p27-deficient mice. Two-week angiotensin II (1500 ng/kg per minute SC) infusion elicited similar degrees of elevation in systolic blood pressure in wild-type mice (159+/-5 mm Hg) and p27-deficient mice (157+/-5 mm Hg; P>0.05). Angiotensin II infusion to wild-type mice resulted in increases in the medial thickness of aorta, proliferating cell number, and monocyte/macrophage infiltration within the vasculature. In p27-deficient mice, however, these changes were more prominent than those in wild-type mice. Treatment of wild-type mice with fasudil, a selective Rho-kinase inhibitor, did not alter blood pressure but significantly upregulated p27 expression, decreased medial thickness of aorta, reduced proliferating cell number, and prevented monocyte/macrophage infiltration. These protective effects of fasudil were attenuated in p27-deficient mice. In conclusion, p27 constitutes an important modulator of angiotensin II-induced monocyte/macrophage infiltration and vascular remodeling, which is mediated in part by Rho-kinase stimulation. Inhibition of Rho-kinase activity improves angiotensin II-induced vascular injury through p27-dependent and p27-independent mechanisms. (Keyword) Angiotensin II / Hypertension, experimental / Macrophages / Muscle, smooth, vascular / Remodeling (Link to Publication Site) ● Publication site (DOI): 10.1161/01.HYP.0000153316.59262.79 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15699465 ● Summary page in Scopus @ Elsevier: 2-s2.0-20144366571 (DOI: 10.1161/01.HYP.0000153316.59262.79, PubMed: 15699465, Elsevier: Scopus)

Proceeding of Domestic Conference:

1.	Masanori Tamaki, Eriko Shibata, 西岡里香, 西岡聡, 松原由紀子, Motoyuki Tamaki, 田蒔正治, Kazuhiro Hasegawa, Kojiro Nagai and Shu Wakino : ESAからロキサデュスタットへ切り替えた保存期CKD症例の解析, Jun. 2024.
2.	Shu Wakino, 柴田理恵子, Kazuhiro Hasegawa, Masanori Tamaki, Masanori Minato, Taizo Inagaki, 宮上慎司, 多田美穂 and Ichiro Hashimoto : 皮膚虚血・潰瘍病変患者における血中亜鉛濃度の意義, 第53回徳島透析療法研究会, Dec. 2023.
3.	Shu Wakino and Kazuhiro Hasegawa : 教育講演糖尿病性腎臓病の治療の進歩, 日本内科学会雑誌, 112, 9, 1680-1689, Sep. 2023. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520016184419352832 (CiNii: 1520016184419352832)
4.	Shu Wakino, Eriko Shibata, Masanori Minato, Ikuko Shimizu and Kazuhiro Hasegawa : 皮膚潰瘍病変患者における血中亜鉛濃度の意義, Journal of Japanese Society for Dialysis Therapy, 56, Suppl.1, 566, May 2023.
5.	Shu Wakino, Kazuhiro Hasegawa and Masanori Tamaki : AKD(acute kidney disease and disorders)を考える透析導入阻止のためのAKD治療戦略, Japanese Journal of Nephrology, 65, 3, 231, May 2023.
6.	Kazuhiro Hasegawa, Masanori Tamaki and Shu Wakino : 心血管内分泌の新知見尿細管糸球体連関とDKD, Folia endocrinologica Japonica, 99, 1, 171, May 2023.
7.	Masanori Minato, Ikuko Shimizu, Masanori Tamaki, Kazuhiro Hasegawa and Shu Wakino : 長時間のAPDにより至適透析を得た重度の精神発達遅滞を有する一例, Journal of Japanese Society for Dialysis Therapy, 56, Suppl.1, 563, 2023.
8.	Kazuhiro Hasegawa, Masanori Tamaki and Shu Wakino : 時間空間的ネットワークで考えるDKDの基礎研究尿細管糸球体クロストークとDKD, Japanese Journal of Nephrology, 64, 6-W, 696, Oct. 2022.
9.	Masanori Tamaki, 宮上慎司, Ikuko Shimizu, 山口純代, Masanori Minato, Sayo Ueda, Eriko Shibata, Kazuhiro Hasegawa and Shu Wakino : ロキサデュスタット投与後に奇異性脳塞栓を発症した1例, Japanese Journal of Nephrology, 64, 6-W, 719, Oct. 2022.
10.	宮上慎司, Masanori Tamaki, Ikuko Shimizu, 山口純代, Masanori Minato, Sayo Ueda, Eriko Shibata, Kazuhiro Hasegawa and Shu Wakino : コロナウィルスワクチン後発症した悪性腎硬化症の一例, Japanese Journal of Nephrology, 64, 6-W, 719, Oct. 2022.
11.	Kazuhiro Hasegawa, Masanori Tamaki, 坂巻裕介 and Shu Wakino : 腎臓病治療に対する新たな切り口 DMミトコンドリア機能改善薬やNADがDKDのみならず腎臓病への切り口となる可能性, Japanese Journal of Nephrology, 64, 3, 189, May 2022.
12.	Shu Wakino, Kazuhiro Hasegawa and 伊藤裕 : DKDに立ち向かう-これまでの100年とこれからの未来- DKD基礎研究の歩みと先端医療, Japanese Journal of Nephrology, 64, 3, 189, May 2022.
13.	Kazuhiro Hasegawa, Masanori Tamaki, 坂巻裕介 and Shu Wakino : NMN消費酵素Nmnatのポドサイト発現調節はE-boxへのepigenetic制御が担う, Japanese Journal of Nephrology, 64, 3, 228, May 2022.
14.	Masanori Tamaki, 宮上慎司, Ikuko Shimizu, 山口純代, Masanori Minato, Sayo Ueda, Eriko Shibata, Motoyuki Tamaki, Motoyuki Tamaki, Kazuhiro Hasegawa, Kojiro Nagai and Shu Wakino : ESAからロキサデュスタットへ切り替えた保存期CKD症例の解析, Japanese Journal of Nephrology, 64, 3, 257, May 2022.
15.	Kazuhiro Hasegawa, Masanori Tamaki, 坂巻裕介 and Shu Wakino : FSGSへのNMN短期集中投与はNMN・NAD消費酵素の暴走連関を抑制し糸球体硬化を抑止する, Japanese Journal of Nephrology, 64, 3, 263, May 2022.
16.	Sayo Ueda, Eriko Shibata, Masanori Tamaki, Masanori Minato, 岩城真帆, Ikuko Shimizu, 山口純代, 宮上慎司, Kazuhiro Hasegawa and Shu Wakino : 急性間質性腎炎を認めた敗血症性AKIの症例, Journal of Japanese Society for Dialysis Therapy, 55, Suppl.1, 507, May 2022.
17.	Masanori Tamaki, 宮上慎司, 岩城真帆, Ikuko Shimizu, 山口純代, Masanori Minato, Sayo Ueda, Eriko Shibata, Kojiro Nagai, Kazuhiro Hasegawa and Shu Wakino : 腹膜透析導入後に膵癌を発症した1例, Journal of Japanese Society for Dialysis Therapy, 55, Suppl.1, 631, May 2022.
18.	Ikuko Shimizu, Masanori Tamaki, 宮上慎司, 山口純代, Masanori Minato, Sayo Ueda, Eriko Shibata, Kazuhiro Hasegawa and Shu Wakino : 慢性大動脈解離に伴う慢性DICのため腎代替療法導入に苦慮した1例, Journal of Japanese Society for Dialysis Therapy, 55, Suppl.1, 663, May 2022.
19.	Masanori Tamaki, 宮上慎司, 岩城真帆, 清水郁子, 山口純代, 湊将典, Sayo Ueda, Eriko Shibata, Kazuhiro Hasegawa, Kojiro Nagai and Shu Wakino : 膵癌を合併した腹膜透析患者の1例, 第27回日本腹膜透析医学会学術集会・総会, Oct. 2021.

Et cetera, Workshop:

1.	Masanori Tamaki, 湊将典, 宮上慎司, 岩城真帆, 清水郁子, 山口純代, Sayo Ueda, Eriko Shibata, Kazuhiro Hasegawa and Shu Wakino : ステントグラフト留置術がAVG頻回閉塞に有用であった一例, 第55回四国透析療法研究会, Oct. 2021.
2.	遠藤理子, 宮上慎司, 湊将典, Masanori Tamaki, 岩城真帆, 清水郁子, 山口純代, Sayo Ueda, Eriko Shibata, Kazuhiro Hasegawa and Shu Wakino : 膜性腎症に合併したIgG4関連腎臓病の一例, 第263回徳島医学会, Aug. 2021.

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

多元的フェロトーシス治療に基づく慢性腎臓病治療戦略の開発 (Project/Area Number: 23K07674 )
Role of NMN transporter in distal-proximal tubule interplay (Project/Area Number: 22K08354 )
Spiral progression of DNA damage repair, epigenetic alterations and metabolic changes in metabolic kidney diseases (Project/Area Number: 20H00535 )
Nampt regulates extracellular matrix composition in DKD (Project/Area Number: 19K08732 )
The significant role of the kidney as a central organ for metabolic organ interrelationship (Project/Area Number: 17H01562 )
The pathophysiology of diabetic tubulopathy and therapeutic application (Project/Area Number: 16H05315 )
Sirt1 and NMN mediate the tubular-PEC crosstalk. (Project/Area Number: 15K09272 )
Tubular- glomerular interaction nd metabolic kidney disease (Project/Area Number: 26253053 )
The significance of proximal tubular lesion in diabetic nephropathy and obesity-related glomerulopathy (Project/Area Number: 25293197 )
Claudin-1 overexpression induces the de-differentiation of podocytes. (Project/Area Number: 24591210 )
Kidney-specific overexpression of Sirt1 protects against chronic kidney disease. (Project/Area Number: 22790800 )
DDAH2 enhances insulin secretion in pancreatic islet by local NO production. (Project/Area Number: 20790654 )
DDAH2過剰発現マウス作成による生体におけるDDAH2の機能解析 (Project/Area Number: 18790624 )
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Associate Professor : Hasegawa, Kazuhiro

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Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)