2012 Fiscal Year Final Research Report
An examination of whether the autophagy in the renal tubule cell could be a new therapeutic target of chronic kidney disease.
| Project/Area Number |
22590889
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
UZU Takashi 滋賀医科大学, 医学部, 准教授 (20422884)
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| Project Period (FY) |
2010 – 2012
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| Keywords | 慢性腎臓病 / オートファジー |
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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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