| Project/Area Number |
24591189
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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 | The University of Tokyo |
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Principal Investigator |
WADA Takehiko 東京大学, 医学部附属病院, 講師 (90447409)
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| Co-Investigator(Kenkyū-buntansha) |
NANGAKU Masaomi 東京大学, 医学部附属病院, 教授 (90311620)
INAGI Reiko 東京大学, 医学部附属病院, 准教授 (50232509)
TANAKA Tetsuhiro 東京大学, 医学部附属病院, 講師 (90508079)
OHSE Takamoto 東京大学, 医学部附属病院, その他 (10568447)
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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 |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 糸球体足細胞 / 小胞体ストレス / 細胞骨格 / 蛋白尿 / オートファジー |
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| Outline of Final Research Achievements |
We investigated how podocytes, which are critical players in glomerular filtration barrier, maintain their homeostasis against various stresses. In this study, we focused on the role of NAD+-dependent deacetylase SIRT1 in the podocyte homeostasis, on the basis of the finding that actin cytoskeleton was deranged in response to oxidative stress. After the induction of experimental nephritis, podocyte-specific SIRT1 deficient mice showed more severe renal injury compared with wild-type mice. Enhanced actin cytoskeleton derangement was observed in the podocytes with downregulated SIRT1 activities. Interestingly, we found that intracellular localization of cortactin, which is associated with actin polymerization, was altered in association with its deacetylation. Our data suggested that deacetylation of cortactin by SIRT1 might play an important role in the maintenance of podocyte cytoskeleton.
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