in vitro and in vivo [53]. The mechanism of PPARγ inhibition in human HSC by ethanol metabolism is rather complex. We found that acetaldehyde inhibits PPARγ by a MAPK mediated phosphorylation on Ser84. The phosphorylation of PPARγ was demonstrated to be dependent on a pathway involving c-Abl, PKCδ, and ERK1/2, and to be initiated by acetaldehyde through a H2O2 dependent mechanism [54]. The signalling axis acetaldehyde-H2O2-PKC-ERK1/2 in mediating the pro-fibrogenic response of HSC is well established [55–57], and H2O2 produced in Kupffer cells induces collagen deposition by HSC [58]. Therefore, inhibition of PPARγ by phosphorylation can potentially occur as a consequence of several diverse processes taking place during the ethanol-induced liver injury.
