2014 Fiscal Year Final Research Report
Claudin-1 overexpression induces the de-differentiation of podocytes.
| Project/Area Number |
24591210
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | 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 |
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Keywords | 糖尿病性腎症 |
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| Outline of Final Research Achievements |
The protective role of Sirt1 in renal damage was investigated. Sirt1 in proximal tubules (PT) was downregulated before albuminuria occurred in streptozotocin-induced or obese-type (db/db) diabetes mellitus (DM) mice. PT-specific Sirt1 transgenic (TG) and knockout (KO) mice showed prevention and aggravation of glomerular changes in DM, respectively, and non-diabetic KO mice already exhibited albuminuria, suggesting that Sirt1 in PT affects glomerular function. Downregulation of Sirt1 and upregulation of the tight junction protein claudin-1 by Sirt1-mediated epigenetic regulation in podocytes contributed to albuminuria. We also demonstrated retrograde interplay from PT to glomeruli through NMN from conditioned medium, measurement of the auto-fluorescence of photoactivatable NMN, and injection of fluorescently labeled NMN. Sirt1 in PT protects against albuminuria in DM through maintaining NMN levels around glomeruli and controlling podocyte function.
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| Free Research Field |
腎臓内科学
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