| Project/Area Number |
18K07980
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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 53010:Gastroenterology-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
鈴木 悠地 岩手医科大学, 医学部, 助教 (00779332)
滝川 康裕 岩手医科大学, 医学部, 教授 (50254751)
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
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| Keywords | カスパーゼ非依存性細胞死 / フルクトース / 不飽和脂肪酸 / 活性酸素種 / MLKLリン酸化 / Hemoxygenase-1 / リゾリン脂質アシル基転移酵素 / 非アルコール性脂肪肝炎 / 非アルコール性脂肪肝 / 非アルコール性脂肪性肝疾患 / アポトーシス / 非アポトーシス細胞死 |
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| Outline of Final Research Achievements |
To regulate liver inflammation in patients with obesity-related non-alcoholic fatty liver disease (NAFLD), we aim mechanism of hepatocyte death which is a cause of inflammation. Unsaturated fatty acid induced caspase-independent cell death via production of reactive oxygen spices (ROS) at hepatocyte cell-line with fructose which was known as cause of obesity. ROS production and caspase-independent cell death were characterized as protein expression of hemoxygenase-1 and phosphorylation of MLKL. Furthermore, increase ROS production and caspase-independent cell death was found in mice which fed with high fat diet and supplementation of sucrose. In liver of patients with NAFLD, ROS production positively correlated with prevalence of number of hepatocytes with caspase-independent death. To control liver inflammation, ROS-induced caspase-independent cell death may be a therapeutic target in pathophysiology of NAFLD.
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| Academic Significance and Societal Importance of the Research Achievements |
肝硬変の原因として増加している非アルコール性脂肪性肝疾患の細胞死の新たな機序を明らかにした。本研究では、比較的毒性が低いとされていた不飽和脂肪酸も、フルクトース過多の環境では強く肝細胞死を誘導することが培養細胞でわかった。更に、マウス、ヒト肝臓でも同様の肝細胞死が確認できたことから、果糖および不飽和脂肪酸の新たな肝細胞障害機序が明らかにできた。
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