| 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
|
| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Liver Fibrosis / Protease Inhibitor / TGF-β / Hepatic Stellate Cell / Collagen |
|---|
| 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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