The significance of proximal tubular lesion in diabetic nephropathy and obesity-related glomerulopathy
| Project/Area Number |
25293197
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Keio University |
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Principal Investigator |
Wakino Shu 慶應義塾大学, 医学部, 准教授 (50265823)
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| Co-Investigator(Kenkyū-buntansha) |
Hiroshi Itoh 慶應義塾大学, 医学部, 教授 (40252457)
Hirobumi Tokuyama 慶應義塾大学, 医学部, 専任講師 (50276250)
Kazuhiro Hasegawa 慶應義塾大学, 医学部, 助教 (30424162)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | 糖尿病性腎症 / 肥満関連腎症 / Sirt1 / Rhoキナーゼ / iNAMPT / NMN / ミトコンドリア / 虚血 / PHD2 / SGLT2 / 肥満 / Rho / Sirtuin / 近位尿細管 / podocyte / アルブミン尿 / インスリン受容体 |
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| Outline of Final Research Achievements |
We examined our hypothesis of tubule-podocyte communication by using proximal tubules (PT)-specific gene engineered mice. PT-specific Sirt1 deficient mice were crossed with db/db mice, which exhibited aggravated albuminuria. NMN, putative mediator of this interplay, was demonstrated to flow from PT to podocytes by photosensitive labelling. We also demonstrated that Sirt1 in PT have a role in the differentiation of parietal epithelial cells and in renal fibrosis by the regulation of iNAMPT. Proximal tubules specific dominant negative RhoA transgenic mice exhibited a decrease Rho/Rho kinase activation by high fat diet, which resulted in the decrease in albuminuria, tubular damages, and the proliferation and hypertrophy of PT cells. The downregulation of cell cycle regulator, p27 contributed to this change. These results suggested PT damage affects glomerular damages, which represent tubule-podocyte communication in diabetic nephropathy and obesity-induced glomerulopathy.
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] Insulin resistance in chronic kidney disease is ameliorated by spironolactone in rats and humans.2014
Author(s)
Hosoya K, Minakuchi H, Wakino S (Corresponding Author), Fujimura K, Hasegawa K, Komatsu M, Yoshifuji A, Futatsugi K, Shinozuka K, Washida N, Kanda T, Tokuyama H, Hayashi K, Itoh H.
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Journal Title
Kidney Int
Volume: 87
Issue: 4
Pages: 749-60
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Renal tubular Sirt1 attenuates diabetic albuminuria by epigenetically suppressing Claudin-1 overexpression in podocytes.2013
Author(s)
Hasegawa K, Wakino S, Simic P, Sakamaki Y, Minakuchi H, Fujimura K, Hosoya K, Komatsu M, Kaneko Y, Kanda T, Kubota E, Tokuyama H, Hayashi K, Guarente L, Itoh H.
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Journal Title
Nature Medicine
Volume: Nov;19(11)
Issue: 11
Pages: 1496-504
DOI
NAID
Related Report
Peer Reviewed
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