To study the fibrogenic action of ethanol in vitro we used a co-culture system of freshly isolated hepatocytes and a liver stellate cell line (CFSC- 2G) developed in our laboratory. Our results show that in this co-culture system ethanol induces the expression of αl(I) procollagen mRNA in a dose- and time-dependent manner. This effect of ethanol was due to its metabolism by alcohol dehydrogenase since 4-methylpyrazole prevented the ethanol- mediated increase in α 1(I) procollagen mRNA. Ethanol was more efficient than acetaldehyde in inducing α 1(I) procollagen mRNA expression and its effect was protein synthesis-independent. Transfection of either hepatocytes or liver stellate cells with a reporter gene, chloramphenicol acetyl transferase (CAT), driven by 3700 bp of the mouse α 1(I) procollagen promoter demonstrated that only LSC expressed significant CAT activity and that this activity was enhanced by ethanol. Overall, our results suggest that this co-culture system is a useful model to study alcohol-induced fibrogenesis in vitro and that mechanisms other than acetaldehyde formation may also play an important role in alcohol-induced fibrogenesis.
Fontana, L., Jerez, D., Rojas-Valencia, L., Solís-Herruzo, J. A., Greenwel, P., & Rojkind, M. (1997). Ethanol induces the expression of α 1(I) procollagen mRNA in a co- culture system containing a liver stellate cell-line and freshly isolated hepatocytes. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1362(2–3), 135–144. https://doi.org/10.1016/S0925-4439(97)00056-2