Modulation of gene expression of transforming growth factor-α by ethanol in ethano-exposed hepatocytes

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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.