Ethanol Induces Transforming Growth Factor-α Expression in Hepatocytes, Leading to Stimulation of Collagen Synthesis by Hepatic Stellate Cells
Article first published online: 3 MAY 2006
Alcoholism: Clinical and Experimental Research
Volume 27, Issue Supplement s1, pages 58S–63S, August 2003
How to Cite
Kato, J., Sato, Y., Inui, N., Nakano, Y., Takimoto, R., Takada, K., Kobune, M., Kuroiwa, G., Miyake, S., Kohgo, Y. and Niitsu, Y. (2003), Ethanol Induces Transforming Growth Factor-α Expression in Hepatocytes, Leading to Stimulation of Collagen Synthesis by Hepatic Stellate Cells. Alcoholism: Clinical and Experimental Research, 27: 58S–63S. doi: 10.1097/01.ALC.0000078614.44983.97
- Issue published online: 3 MAY 2006
- Article first published online: 3 MAY 2006
- Received for publication May 9, 2003; accepted May 9, 2003.
- 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.