| Project/Area Number |
25860691
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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 |
Kidney internal medicine
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 糖尿病腎症 / Rho-kinase / ROCK2 / 糸球体上皮細胞 / Notch / 糖尿病 / アポトーシス / 糸球体硬化 / メサンギウム細胞 |
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| Outline of Final Research Achievements |
The small GTPase Rho and its downstream effector Rho-kinase, regulate a number of cellular processes, including organization of the actin cytoskeleton, cell adhesion and migration. Studies from our laboratory and others have shown that pharmacological inhibition of Rho-kinase in experimental diabetic models results in a significant reduction in albuminuria and glomerulosclerosis.
In this project, we investigated the role of Rho-kinase in the Notch pathway and glomerular podocyte loss under diabetic conditions. The activated Notch signaling and podocyte apoptosis were inhibited by the pharmacological or genetic blockade of Rho-kinase. Moreover, we found that ROCK2 isoform made dominant contribution to the regulation of Notch pathway. Collectively, these findings identify ROCK2 as a critical regulator of podocyte injury and the progression of diabetic nephropathy.
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