The significance of proximal tubular lesion in diabetic nephropathy and obesity-related glomerulopathy

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293197
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: Wakino Shu 慶應義塾大学, 医学部, 准教授 (50265823)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 糖尿病性腎症 / 肥満関連腎症 / Sirt1 / Rhoキナーゼ / iNAMPT / NMN

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.

Free Research Field

腎臓病学、内分泌代謝病学