Figure 2.

Possible mechanisms for the direct profibrotic effects of ethanol on hepatic stellate cells. Acetaldehyde, together with ethanol or acetaldehyde-derived oxidative stress, induces latent TGFβ1 and TGFβ receptor activation that subsequently leads to Smad3/4 activation and binding to the promoter of collagen I genes. PKC and/or PI-3K kinases are also activated by acetaldehyde. Both kinase systems activate their downstream components, including ERK1/2 and JNK. As a result, C/EBP, NF-1 and/or BTEB transcription factors are activated and therefore up-regulate collagen I gene transcription.