2022 Fiscal Year Final Research Report
Elucidation of growth factor-mediated repair mechanism toward non-alcoholic steatohepatitis and its application for therapeutic use
Project/Area Number |
20K11589
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 59040:Nutrition science and health science-related
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Research Institution | Toho University |
Principal Investigator |
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | 肝線維化 / 線維芽細胞増殖因子 / 非アルコール性脂肪肝炎 |
Outline of Final Research Achievements |
Nonalcoholic steatohepatitis (NASH) is a disease with increasing prevalence worldwide. Among NASH symptoms, liver fibrosis has the greatest impact on life prognosis. We analyzed NASH model mice that we established independently, and found that FGF18, one member of the fibroblast growth factor (FGF) family, is involved in liver fibrosis during NASH exacerbation. Furthermore, we generated hepatocyte-specific FGF18 overexpressing mice, and these mice exerted spontaneous hepatomegaly and hepatic fibrosis under normal rearing conditions. Therefore, FGF18 plays a key role in liver fibrosis, suggesting that it may be a therapeutic target for anti-hepatic fibrosis drugs.
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Free Research Field |
生化学
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Academic Significance and Societal Importance of the Research Achievements |
肝線維化は様々な肝疾患で起こり生命予後に大きく影響するため、発症メカニズムの解明と治療薬の開発は急務である。肝線維化の病態モデル動物としては、マウスに四塩化炭素などを腹腔投与し炎症を誘発して線維化を誘導する実験系が頻用されるが、薬物の標的が炎症なのか線維化なのかを判別するのが困難である。本研究で作製した肝細胞特異的FGF18過剰発現マウスは炎症を介さずに直接線維化を誘導できることから、新たな病態モデル動物として肝線維化メカニズムの解明および治療薬のスクリーニングに利用できると期待される。
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