| Project/Area Number |
24790768
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | サーチュイン / 創傷治癒 / 線維化 / TGFβ受容体 / TGF-β |
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| Research Abstract |
We investigated the role of Sirt7 in cardiovascular tissue repair process. In wild type (WT) mice, Sirt7 expression increased in response to acute cardiovascular injury. Sirt7 deficient (Sirt7-/-) mice showed susceptibility to cardiac rupture after MI, delayed blood flow recovery following hindlimb ischemia, and impaired wound healing after acute skin injury, compared to WT mice. In vitro, knockdown of endogenous Sirt7 by siRNA attenuated tube formation, proliferation and migration of endothelial cells. Fibroblasts isolated from Sirt7-/- mice showed reduced smad2 phosphorylation upon TGF-b stimulation compared with WT mice, and these changes were accompanied by reduction in TGF-b receptor 1 (Tb-RI) protein. Tb-RI protein level in the lipid raft fraction was higher in Sirt7-/- dermal fibroblasts than WT. These data indicate that Sirt7 contributes to tissue repair processes by maintaining TGF-b receptor protein level.
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