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 |
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| Research Field |
Virology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
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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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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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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 / コラーゲン線維合成系 |
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| 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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Report
(5 results)
Research Products
(9 results)
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[Journal Article] Selective inhibitor of Wnt/β-catenin/CBP signaling ameliorates hepatitis C virus-induced liver fibrosis in mouse model2017
Author(s)
Yuko Tokunaga, Yosuke Osawa, Takahiro Ohtsuki, Yukiko Hayashi, Kenzaburo Yamaji, Daisuke Yamane, Mitsuko Hara, Keisuke Munekata, Kyoko Tsukiyama-Kohara, Tsunekazu Hishima, Soichi Kojima, Kiminori Kimura, and *Michinori Kohara
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Journal Title
Scientific Reports
Volume: 7
Issue: 1
Pages: 325-325
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Selective inhibitor of Wnt/beta-catenin/CBP signaling ameliorates hepatitis C virus-induced liver fibrosis2014
Author(s)
Tokunaga Y, Kimura K, Ohtsuki T, Hayashi Y, Hara M, Munekata K, Hishima T, Kouji H, Kojima S, Kohara M
Organizer
21th International Symposium on Hepatitis C Virus and Related Viruses
Place of Presentation
Banff, Canada
Year and Date
2014-09-07 – 2014-09-11
Related Report
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