2016 Fiscal Year Final Research Report
Strategies aimed at modulating autophagy for treating kidney diseases
| Project/Area Number |
15H06371
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Kidney internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2015-08-28 – 2017-03-31
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| Keywords | オートファジー / フラックス / 近位尿細管 / 老化 / Rubicon / クロロキン |
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| Outline of Final Research Achievements |
Autophagy plays an essential role for cellular homeostasis. Here, we established the methods for monitoring autophagic flux in vivo by using GFP-LC3 transgenic mice and tamoxifen-inducible proximal tubule-specific autophagy-deficient mice. Using the methods, we investigated the impact of altered autophagic flux in kidney aging. Furthermore, we newly established mice models in which autophagic flux is genetically (Rubicon, a Beclin1-interacting negative regulator for autophagosome-lysosome fusion, knockout mice) and pharmacologically(omega-3 fatty acid, EPA) enhanced. Proximal tubule-specific Rubicon knockout mice showed high autophagic flux in basal and stressed conditions and exhibited significant improvement of kidney injury in some choronic kidey disease models. Also, EPA attenuated renal lipotoxicity by improving autophagic flux in obese mice kidneys. Modulating autophagic flux would be a potentially important therapeutic target for regulating progression of kidney diseases.
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| Free Research Field |
腎臓内科学
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