| Project/Area Number |
26860634
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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 |
Kidney internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2014: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 尿酸腎症 / 近位尿細管 / オートファジー / リソソーム傷害 / インフラマソーム / NLRP3 |
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| Outline of Final Research Achievements |
In this study, we demonstrated that in hyperuricemic mice model, NLRP3 inflammasome was more activated in proximal-tubule specific autophagy-deficient mice than in autophagy competent mice. Furthermore, infiltration of macrophage and fibrotic changes were exacerbated in proximal-tubule specific autophagy-deficient mice. Our in vitro study indicated that more ROS production was induced in high concentration of uric acid and more LMP (Lysosomal Membrane Permeabilization) was triggered during MSU crystals exposure in autophagy deficient proximal tubular cells compared with in autophagy competent cells. These results suggest that NLRP3 inflammasome is involved in hyperuricemic nephropathy and that autophagy guards against hyperuricemic nephropathy by alleviating ROS production and LMP. Upregulation of autophagy might be promising strategy for hyeruricemic nephropathy.
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