1998 Fiscal Year Final Research Report Summary
ELUCIDATION OF SIGNIFICANCE OF c-met EXPRESSION IN ACTIVATED HEPATIC STELLATE GELLS AND ITS APPLICATION OF THERAPEUTIC STRATEGY
| Project/Area Number |
09670517
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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 | UNIVERSITY OF TOKYO |
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Principal Investigator |
IKEDA Hitoshi UNIV.OF TOKYO,FACULTY OF MEDICINE,INSTRUCTOR, 医学部・附属病院, 助手 (80202422)
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| Co-Investigator(Kenkyū-buntansha) |
NAGOSHI Sumiko UNIV.OF TOKYO,FACULTY OF MEDICINE,TRAINEE, 医学部・附属病院, 医員
OHNO Akihiko UNIV.OF TOKYO,FACULTY OF MEDICINE,INSTRUCTOR, 医学部・附属病院, 助手 (30223902)
OGATA Itsuro UNIV.OF TOKYO,FACULTY OF MEDICINE,INSTRUCTOR, 医学部・附属病院, 助手 (80169169)
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| Project Period (FY) |
1997 – 1998
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| Keywords | ITO CELLS / HGF / c-met / TGFbeta / STELLATE CELLS |
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| Research Abstract |
(1) We have found that activated rat hepatic stellate cells express c-met, the receptor of hepatocyte growth factor (HGF). In culture-activated stellate cells, c-met expression was determined by Northern and Western hint analyses. Specific binding of HGF to activated stellate cells was determined, and Scatchard analysis indicated an apparent K_d of 1.5 nM.Moreover, c-met mRNA expression was detected in stellate cells isolated from rats treated with carbon tetrachloride for 8 weeks.
(2) In culture-activated stellate cells, HGF increased c-met mRNA level. HGF enhanced DNA synthesis and transforming growth factor beta1 (TGFbeta1) production by the cells, whereas HGF did not affect collagen synthesis nor smooth muscle alpha-actin expression.
(3) Considering that HGF is produced by stellate cells, HGF may affect those cells by autocrine mechanism. Because the proliferation of stellate cells is one of the main features of hepatic fibrosis and TGFbeta1 is known as a fibrogenic cytokine, our results suggest that HGF might accelerate hepatic fibrogenesis. However, recent evidence has revealed that HGF abrogates hepatic fibrosis in rats treated with carbon tetrachloride or dimethylnitrosamine. We speculate that this inhibitory effect of HGF on hepatic fibrosis may not be due to the direct action on stellate cells, but to the indirect action through, say possible cytoprotective effect of HGF.
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