| Project/Area Number |
18KT0065
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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 | 特設分野 |
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| Research Field |
Complex Systems Disease Theory
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
中川 嘉 富山大学, 学術研究部薬学・和漢系, 教授 (80361351)
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| Project Period (FY) |
2018-07-18 – 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: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 生活習慣病 / CREBH / 脂肪肝 / 肝炎 / lncRNA / SREBP / エクソソーム / non-coding RNA / マイクロRNA / 代謝産物 |
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| Outline of Final Research Achievements |
It is judged as a disease after going through a state "not sick" that cannot be clearly judged as a disease in the progression of the pathological condition of a lifestyle-related disease. Therefore, it is necessary to define a biomarker that determines the condition of the pathological condition. CREBH is a transcription factor that regulates lipid metabolism, and CREBH-deficient mice exacerbate and exacerbate diet-induced fatty liver. At that time, it was found that one of the non-coding RNAs, H19, was abnormally increased in the liver, and that some of the inflammatory cytokines were also increased. In addition, liver-specific CREBH overexpressing mice were generated using the Cre-LoxP system using the CRISPR / Cas9 system. The mice showed reduced blood lipids, indicating that CREBH improves lipid metabolism in the liver.
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| Academic Significance and Societal Importance of the Research Achievements |
CREBHは現在まで、知名度のある分子ではなかった。しかしながら、CREBH欠損マウスが脂質代謝異常から脂肪肝を呈する新たなモデルマウスであることを示した学術的、社会的意義は大きい。また、その病態発症のメカニズムにエクソソームで細胞間、組織間を移動し、病態発症に関与すると報告のあるnon coding RNA, H19が関与することを示唆する結果を得た。新たな病態マーカーになりえる因子の同定は、今後の脂肪肝の治療戦略に新たな道筋を示したと言え、社会的意義は大きい。
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