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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| Project Status |
Completed (Fiscal Year 2014)
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| 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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| Keywords | 糖尿病性腎症 / 腎臓学 / ＳＩＲＴ１ |
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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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Report
(4 results)
Research Products
(12 results)
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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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