Ethanol induces transforming growth factor-α expression in hepatocytes, leading to stimulation of collagen synthesis by hepatic stellate cells

被引:23
作者
Kato, J
Sato, Y
Inui, N
Nakano, Y
Takimoto, R
Takada, K
Kobune, M
Kuroiwa, G
Miyake, S
Kohgo, Y
Niitsu, Y
机构
[1] Sapporo Med Univ, Sch Med, Dept Internal Med 4, Chuo Ku, Sapporo, Hokkaido 0608543, Japan
[2] Asahikawa Med Coll, Dept Internal Med 3, Asahikawa, Hokkaido 078, Japan
关键词
transforming growth factor-alpha; alcoholic liver disease; liver fibrosis; hepatic stellate cells;
D O I
10.1097/01.ALC.0000078614.44983.97
中图分类号
R194 [卫生标准、卫生检查、医药管理];
学科分类号
摘要
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 similar to6000 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)-alpha was assessed by enzyme-linked immunosorbent assay. TGF-alpha 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-alpha antibodies. Western blot analysis showed increased TGF-a protein expression in ethanol-treated HepG2 cells. TGF-alpha in conditioned medium from ethanol-exposed HepG2 cells stimulated type-l collagen messenger RNA expression in rat hepatic stellate cells. Conclusions: These results suggest that TGF-alpha derived from ethanol-exposed hepatocytes may contribute to the development of hepatic fibrosis in alcoholic liver diseases.
引用
收藏
页码:58S / 63S
页数:6
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