2017 Fiscal Year Final Research Report
Analysis of mechanism of anti-fibrotic effect by a liver cirrhosis treatment drug candidate
Project/Area Number |
26860312
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Virology
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Research Institution | Tokyo Metropolitan Institute of Medical Science |
Principal Investigator |
MUNEKATA (TOKUNAGA) Yuko (徳永優子) 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (80555011)
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Research Collaborator |
HAYASHI Yukiko
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Project Period (FY) |
2014-04-01 – 2018-03-31
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Keywords | 新規肝硬変治療薬候補 / 脱線維化作用 / コラーゲン線維分解系 / マクロファージ / 好中球 / マトリックスメタロプロテアーゼ / 1細胞トランスクリプトーム解析 |
Outline of Final Research Achievements |
Chronic hepatitis C virus (HCV) infection is one of the major causes of serious liver diseases, including liver cirrhosis. There are no anti-fibrotic drugs with efficacy against liver cirrhosis. Wnt/β-catenin signaling has been implicated in the pathogenesis of a variety of tissue fibrosis. We showed that ICG-001 derivative, a selective inhibitor of β-catenin/CBP interaction, exhibits the anti-fibrotic activity on HCV-induced fibrosis. In the present study, we investigated the molecular mechanism of the compound using HCV transgenic mouse model. Administration of ICG-001 derivative for 6 weeks led to increased levels of matrix metalloproteinase (MMP)-8, which was shown with mRNA and protein expression, enzymatic activities. The induced intrahepatic neutrophils and macrophages/monocytes were identified as the source of MMP-8. In conclusion, we hypothesize that induction of fibrolytic cells expressing MMP-8 contribute to the remission of fibrosis by ICG-001 derivative.
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Free Research Field |
ウイルス学、分子生物学
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