| Project/Area Number |
26461020
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
上野 隆 順天堂大学, 医学(系)研究科(研究院), 客員教授 (10053373)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | オートファジー / リソソーム / ミトコンドリア / 肝再生 / 脂肪性肝疾患 / 肝脂肪化 / 細胞内代謝 / 小胞体 / 慢性肝炎 |
|---|
| Outline of Final Research Achievements |
We reported that autophagic acidification was altered by a decrease in lysosomal proton pump V-ATPase in hepatocytes from NAFLD. mTOR inhibitor ameliorated V-ATPase expression occluded by hepatic steatosis, followed by recovering acidification and proteolytic activity of autolysosomes. These results indicate that activation of mTOR caused dysregulation of autophagic acidification in NAFLD. Moreover, we found that dysfunction of mitochondrial autophagy increased the mitochondrial proteins not only produce oxidative stress but also inhibit apoptosis. Additionally, we found that Parkin-deficiency represses liver regeneration after partial hepatectomy. Parkin promotes degradation of dysfunctional mitochondria by autophagy; therefore, parkin-deficiency enhanced the mitochondrial dysfunction after partial hepatectomy. These results indicate that the selective removing mitochondria modified by Parkin plays a pivotal role on the maintaining mitochondrial function during liver regeneration.
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