Effects of extracellular signal-regulated kinase on rat cultured hepatic stellate cells stimulated by acetaldehyde.

Objective: To investigate the effects of PD98059 on the cell cycle, cell proliferation, the secretion of type I collagen and expression of transforming growth factor-beta-1 mRNA in rat hepatic stellate cells stimulated by acetaldehyde.

Methods: Rat hepatic stellate cells stimulated by acetaldehyde were incubated with different concentrations of PD98059. The cell cycle was analyzed by flow cytometry. Cell proliferation was assessed by methyl thiazolyl tetrazolium colorimetric assay. The mRNA expression of transforming growth factor-beta-1 was examined by reverse transcriptase polymerase chain reaction. Type I collagen of the culture medium was detected by enzyme-linked immunoadsorbent assay.

Results: Twenty, 50 and 100 micromol/L PD98059 could significantly inhibit the proliferation and provoke a G0/G1-phase arrest of hepatic stellate cells stimulated by acetaldehyde in a dose-dependent manner. The secretion of type I collagen and transforming growth factor-beta-1 mRNA expression of acetaldehyde-induced hepatic stellate cells were markedly inhibited by 50 and 100 micromol/L PD98059, respectively.

Conclusion: Extracellular signal-regulated kinase signal transduction pathway could regulate cell proliferation, the secretion of type I collagen and transforming growth factor-beta-1 mRNA expression of rat hepatic stellate cells stimulated by acetaldehyde. This is most likely related to its regulative effect on the cell cycle.