• Transforming Growth Factor-α;
  • Alcoholic Liver Disease;
  • Liver Fibrosis;
  • Hepatic Stellate Cells

Background: 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 previously found that ethanol exposure causes HepG2 cells to secrete a ∼6000 Da nonheparin-binding polypeptide that stimulates collagen synthesis in human IMR-90 fibroblasts. The aim of the current study was to characterize and identify this factor.

Methods: Concentration of type I procollagen peptide and transforming growth factor (TGF)-α was assessed by enzyme-linked immunosorbent assay. TGF-α protein expression was examined by Western blot. Type I collagen messenger RNA expression in rat hepatic stellate cells was assessed by reverse transcription-polymerase chain reaction.

Results: The collagen-stimulating activity in conditioned media from ethanol-exposed HepG2 cells to stimulate type I procollagen peptide synthesis of IMR-90 cells was specifically inhibited by addition of anti-TGF-α antibodies. Western blot analysis showed increased TGF-α protein expression in ethanol-treated HepG2 cells. TGF-α in conditioned medium from ethanol-exposed HepG2 cells stimulated type-I collagen messenger RNA expression in rat hepatic stellate cells.

Conclusions: These results suggest that TGF-α derived from ethanol-exposed hepatocytes may contribute to the development of hepatic fibrosis in alcoholic liver diseases.