| Project/Area Number |
18K06656
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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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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Osaka University |
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Principal Investigator |
SAKAI EIKO 大阪大学, 薬学研究科, 特任研究員 (60359859)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肝臓 / 脂質 / 酸化ストレス / マイクロRNA / ミトコンドリア / NASH |
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| Outline of Final Research Achievements |
We have previously identified a novel target gene of miR-27b, MAIP1. miR-27b is reported to be unregulated in NASH NAFLD patients. Also we have shown that knockdown of MAIP1 in a cultured hepatocarcinoma cell line induced lipid accumulation as well as down-regulation of oxidative phosphorylations. In this study, we observed that knockdown of MAIP1 resulted in defects of a variety of mitochondrial functions, such as membrane potentials, oxygen consumption rate of complex 1, resulting in increased ROS production and increased lesion in mitochondria genomes. These results suggested potential contribution of decreased MAIP1 expression in NASH/NAFLD.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、MAIP１の発現低下が脂質蓄積だけではなくミトコンドリア機能の低下および酸化ストレスの発生を誘導することを明らかとした。さらに、その原因として電子伝達系機能の阻害があることを示した。これにより、NAHS/NAFLD病態に対して、ミトコンドリア機能の抑制と酸化ストレスを介してMAIP1が寄与する可能性を示した。これらの知見はMAIP1を標的とした創薬・治療法の開発に向けた基盤をなることが期待される。
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