| Project/Area Number |
18K15768
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53010:Gastroenterology-related
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| Research Institution | Tokyo Metropolitan Komagome Hospital (Clinical research laboratory) |
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Principal Investigator |
Kimura Masamichi 東京都立駒込病院(臨床研究室), 肝臓内科, 非常勤医師 (20805262)
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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 |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 肝硬変 / 肝線維化 / NASH / Wntシグナル / 非アルコール性脂肪性肝炎 / 線維化 |
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| Outline of Final Research Achievements |
It is estimated that there are 10 million people in Japan with non-alcoholic steatohepatitis (NAFLD), of which 2 million have non-alcoholic steatohepatitis (NASH) that progresses to cirrhosis and liver cancer. Liver fibrosis in NASH is thought to progress by the action of various factors such as insulin resistance. The purpose of this study was to elucidate the mechanism of liver fibrosis mediated by Wnt / β-catenin pathway in NASH and to analyze the antifibrotic effect of PRI-724, a Wnt / β-catenin inhibitor. PRI-724 also showed an antifibrotic effect in the NASH liver fibrosis model. We also obtained findings on CBP signals in hepatocytes and liver fibrosis .
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| Academic Significance and Societal Importance of the Research Achievements |
申請者らは、Wnt/β-catenin阻害薬であるPRI-724をHCV Tg マウス及びC型肝硬変患者に投与して良好な抗線維化作用を確認した。本研究はHCVとは病態の異なるNASHモデルでの抗線維化作用の検討及びそのメカニズムを解明することを目的とした。結果的にNASHモデルにおいても、PRI-724投与により他の線維化モデルと同様に肝線維化の有意な改善が認められた。またCBP-flox/ALB-Creマウスを樹立し、肝細胞のCBPシグナルが肝線維化に作用する機序に関する新たな知見を得た。抗線維化治療薬が実現すれば、肝不全への進行や肝発がんを予防でき、肝硬変患者の予後の改善が期待される。
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