| Project/Area Number |
23591182
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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 | Chiba University |
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Principal Investigator |
HAMANO Yuki 千葉大学, 医学部附属病院, 助教 (90396680)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Makoto 千葉大学, 大学院医学研究院, 講師 (50241956)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | p53 / Anti-GBM Disease / CDK2 / 18型コラーゲン / エンドスタチン / 糖尿病性腎症 / 血管新生 / 老化 |
|---|
| Research Abstract |
Anti-glomerular basement membrane (GBM) glomerulonephritis (GN) was induced in p53-null (KO) and wild-type (WT) mice. In the experiment to test the effect of pharmacological inhibition of p53, WT mice were administered pifithrin-alpha with the injection of anti-mouse GBM serum. Serum creatinine levels (Scr) were significantly elevated in nephritic KO mice compared with nephritic WT mice. In the kidney of nephritic KO mice, glomerular and interstitial cells were proliferated with extracellular matrix expansion. The proliferative change in the nephritic KO mice was accompanied by the activation of cyclin-dependent kinase 2 (CDK2). Similarly, the pharmacological inhibition of p53 in nephritic WT mice led to the increased cell proliferation and CDK2 activation, which were completely reversed by roscovitine, a selective CDK2 inhibitor. These findings indicate that endogenous p53 inhibits the excessive proliferative responses and regulates extracellular matrix homeostasis during anti-GBM GN.
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