| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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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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