1999 Fiscal Year Final Research Report Summary
Inhibition of Liver Fibrosis by Protease Inhibitors
| Project/Area Number |
09670533
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Gifu University |
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Principal Investigator |
OKUNO Masataka First Department of Internal Medicine Gifu University School of Medicine Assistant Professor, 医学部, 助手 (10204140)
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| Co-Investigator(Kenkyū-buntansha) |
KJIMA Soichi Laboratory of Molecular Cell Sciences Tsukuba Life Science Center The Institute of Physical and Chemical Research Senior Researcher, ライフサイエンス筑波研究センター, 先任研究員 (10202061)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Liver Fibrosis / Protease Inhibitor / TGF-β / Hepatic Stellate Cell / Collagen |
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| Research Abstract |
We investigated the mechanism by which proteases activates transforming growth factor-β (TGF-β) in hepatic stellate cells (HSCs). We found that serine proteases including plasmin and kallikrein activate latent TGF-β both in HSC cultures and in animal experiments. Active TGF-β generated, then, stimulated the synthesis of itself as well as collagen, and suppressed the regeneration of the liver. Therefore, we hypothesized that the suppression of TGF-β activation is an important target in the therapy of hepatic fibrosis. We screened 20 protease inhibitors and obtained two compounds that are effective in suppressing both TGF-β activation and subsequent hepatic fibrosis in animal models.
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Research Products
(19 results)
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[Publications] Okuno M, Kajiwara K, Imai S, Kobayashi T, Honma N, Maki T, Suruga K, Goda T, Takase S, Muto Y, Moriwaki H.: "Perilla oil prevents the excessive growth of visceral adipose tissue in rats via down-regulating adipocyte differentiation."J Nutr. 127. 1752-1757 (1997)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Okuno M, Sato T, Kitamoto T, Imai S, Nagase S, Suzuki Y, Yoshimura H, Moriwaki H, Masushige S, Muto Y, Friedman SL, Kato S, Kojima S.: "Increased 9,13-di-cis-retinoic acid in rat hepatic fibrosis: A potential link between retinoid loss and TGF-β mediated fibrogenesis via RARα activation."J Hepatol. 30. 1073-1080 (1999)
Description
「研究成果報告書概要(欧文)」より
