2016 Fiscal Year Final Research Report
The change of endocytosis receptor expression and its possible role during the progress of proximal tubular injury
| Project/Area Number |
15K19186
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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 |
Laboratory medicine
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Keywords | 近位尿細管 / エンドサイト―シス / メガリン |
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| Outline of Final Research Achievements |
Effects of insulin on megalin expression in proximal tubular cells were evaluated. It was clarified insulin has no effect on megalin expression in HK-2 cells. Then we examined the effect of high glucose on megalin expression. High glucose treatment significantly increased megalin expression in HK-2 cells. Hydrogen peroxide also significantly increased megalin expression. Furthermore, the hydrogen peroxide-induced increase in megalin expression was blocked by treatment with PI3K and Akt inhibitors. In animal experiments, we demonstrate that increased expression of renal cortical megalin and p-Akt accompanies oxidative stress in diabetic rats, prior to albuminuria development. Telmisartan, which is one of RAS inhibitor, treatment prevented the diabetes-induced elevation of oxidative stress, megalin and p-Akt expression. Taken together, our results indicate that oxidative stress increases renal megalin expression via PI3K/Akt pathway in the normoalbuminuric stage of diabetes.
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| Free Research Field |
糖尿病性腎症
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