| Project/Area Number |
13670575
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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 | KURUME UNIVERSITY |
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Principal Investigator |
SAKATA Ryuichiro Kurume University School of Medicine ・ Assistant, 医学部, 助手 (70258424)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Toru Kurume University School of Medicine ・ Assistant, 医学部, 助手 (30341332)
UENO Takato Research Center for Innovative Cancer Therapy of Kurume University ・ Professor, 先端癌治療研究センター, 教授 (70176618)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | catechin / liver fibrosis / liver cirrhosis / hepatic stellate cell / chronic liver disease / 肝繊維化 / PDGFレセプター / MAPK / Erk / MEK / Scatchard Analysis |
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| Research Abstract |
Green tea polyphenols are known to have properties that inhibit the growth of fibroblast cell lines. The activation and proliferation of hepatics stellate cells (HSC) are closely related to the progression of chronic liver diseases. We investigated the inhibitory effect of epigallocatechin gallate (EGCG), the major potential inhibitory component of green tea polyphenols, on the proliferation of HSC. The aim of this study was to clarify the molecular mechanisms of EGCG inhibition of HSC proliferation.
A cultured human hepatic stellate cell line, LI90, was used for this study. The cells were serum-starved and exposed to PDGF (10ng/ml). EGCG was dissolved in basal medium and prepared at 0-50 μM concentrations. Proliferation was determined by BrdU incorporation and cell cycle analysis. EGCG inhibited the cell-proliferation induced by PDGF-BB. EGCG induced S phase inhibition in the cells. PDGF receptor tyrosine phosphorylation was detected using anti-phosphotyrosine antibody. EGCG reduced the phosporylation of the PDGF receptor in a dose-dependent manner. To establish the characters of the antagonism exerter by EGCG, competition studies were carried out with [^<125>I] -PDGF-BB in the presence of EGCG. EGCG blocked PDGF-BB binding to its receptor in a non-competitive manner.
EGCG has an inhibitory effect on PDGF-induced proliferation of HSC, and the non-competitive blocking of PDGF-BB binding to its receptor may be the molecular mechanism behind this effect. Investigation of the effects of EGCG on HSC proliferation may contribute to the development of new prophylactic strategies for the prevention of liver fibrogenesis in chronic liver diseases.
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