| Project/Area Number |
09670560
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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 | SAPPORO MEDICAL UNIVERSITY |
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Principal Investigator |
KATO Junji SAPPORO MEDICAL UNIVERSITY,assistant professor., 医学部, 講師 (20244345)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Minoru SAPPORO MEDICAL UNIVERSITY,Assistant, 医学部, 助手 (60291556)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | Alcoholic liver fibrosis / TGF-alpha / ethanol / Ito cells / HepG2 cells / IMR-90 cells / procollagen peptide C / collagen |
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| Research Abstract |
Although it is well known that hepatic fibrosis develops in alcoholic liver diseases (ALD) without accompanying inflammation, the underlying mechanism is unclear. Using ethanol-exposed human HepG2 hepatoblastoma cells as a model for ALD, we previously found that ethanol exposure causes HepG2 cells to secrete a polypeptide factor which stimulates collagen synthesis in human IMR-90 fibroblasis. The aim of this study was to characterize and identify this factor.
Collagen stimulating activity in conditioned media (CM) from ethanol-exposed HepG2 cells was assessed by its ability to stimulate synthesis of type I procollagen peptide (PIC) in IMR-90 cells. The identity of the factor was tested by the ability of antibodies to various cytokines to deplete collagen stimulating activity from CM.Transforming growth factor (TGF)-alpha in the CM of ethanol-treated HepG2 and serum TGF-alpha levels in patients with ALD were determined using an enzyme-linked immunosorbent assay. The collagen stimulating activity in CM could be depleted by antibody to TGF-alpha. Consistent with this, TGF-alpha in the CM of ethanol-treated HepG2 increased in a time-and dose-dependent manner. Suggesting that TGF-alpha may play a role in ALD, serum TGF-alpha levels in patients with ALD liver fibrosis were significantly higher than in patients with chronic viral hepatitis and viral cirrhosis. In conclusion, TGF-alpha may contribute to the development of hepatic fibrosis in ALD.
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