The role of ROCK2 in the progression of diabetic nephropathy
| 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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Report
(3 results)
Research Products
(14 results)
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[Journal Article] Rho-kinase regulation of TNF-α-induced nuclear translocation of NF-κB RelA/p65 and M-CSF expression via p38 MAPK in mesangial cells.2014
Author(s)
Matoba K, Kawanami D, Tsukamoto M, Kinoshita J, Ito T, Ishizawa S, Kanazawa Y, Yokota T, Murai N, Matsufuji S, Utsunomiya K.
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Journal Title
Am J Physiol Renal Physiol.
Volume: 307
Issue: 5
Pages: F571-F580
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Rho-kinase inhibition prevents the progression of diabetic nephropathy by downregulating hypoxia-inducible factor 1a2013
Author(s)
Matoba K, Kawanami D, Okada R, Tsukamoto M, Kinoshita J, Ito T,Ishizawa S, Kanazawa Y, Yokota Y, Murai N, Matsufuji S, Utsunomiya K.
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Journal Title
Kideny Int
Volume: (in press)
Issue: 3
Pages: 545-554
DOI
Related Report
Peer Reviewed
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