| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Research Abstract |
Autophagy is an intracellular degradation system to protect cells by removing damaged proteins and organelles. We examined the role of autophagy in obesity-mediated exacerbation of proteinuria-induced tubular damages. In non-obese mice, proteinuria induced by intraperitoneal albumin-overload led to mild proximal tubular epithelial cell damage and apoptosis. In contrast, high fat diet-induced obesity suppressed proteinuria-induced autophagy in proximal tubular cells and exacerbated proteinuria-induced proximal cell damage and apoptosis. Proximal tubular cell -specific autophagy-deficient mice developed severe proteinuria-induced proximal tubular cell damage, suggesting that proteinuria-induced autophagy was renoprotectively elicited. Autophagy insufficiency was ameliorated by treatment with the mammalian target of rapamycin (mTOR) inhibitor. These results suggest that a restoration of the renoprotective action of autophagy in proximal tubular epithelial cells become a new therapeutic approach to improve the renal outcome.
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