2000 Fiscal Year Final Research Report Summary
Modulation of gene expression of transforming growth factor-α by ethanol in ethano-exposed hepatocytes
| Project/Area Number |
11670519
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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 professor, 医学部, 助手 (60291556)
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| Project Period (FY) |
1999 – 2000
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| Keywords | Alcoholic liver fibrosis / TGF-α / ethanol / Hepatic ctellate cells / HepG2 cells / IMR-90 cells / NF-kB / Oxidative damage |
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| Research Abstract |
Liver fibrosis often develops in alcoholic liver diseases without accompanying inflammation, however the underlying mechanism is unclear. Using ethanol-exposed human HepG2 hepatoblastoma cells as a model for alcoholic liver diseases, we found previously that ethanol exposure causes HepG2 cells to secrete transforming growth factor-α (TGF-α) which stimulates collagen synthesis in human IMR-90 fibroblasts and rat hepatic stellate cells. The aim of this study was to investigate the mechanism of TGF-α gene expression by ethanol. TGF-α mRNA and protein expression by Northern and Western bolt, respectively. Gel mobility shift assay for NF-kB for the promotor region of TGF-α gene was examined. Northern and Western blot analyses showed increased TGF-α mRNA and protein expression in ethanol-treated HepG2 cells. Ethanol-treatment increased degradation of IkB and enhanced TGF-α transcription via NF-kB.Ethano-induced NF-kB activation and TGF-α transcription were blocked in the presence of anti-oxidant, NAC, suggesting that production of reactive oxygen species is inplicated in this signaling. In conclusion, TGF-α is considered to contribute to the development of hepatic fibrosis in alcoholic liver diseases.
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