PPARgamma mRNA expression was stable during culture-activation of HSCs. However, PPARgamma protein was only found in quiescent HSCs but not in fully activated cells. Exposure of HSCs to PPARgamma agonists maintained the expression of PPARgamma, and transactivated this transcription factor as demonstrated by gelshift assay and by induction of CD36, a PPARgamma-regulated gene. However, PPARgamma ligands did not alter the induction of Collagen-I mRNA or alpha-smooth muscle actin (alpha-SMA) in cultured HSCs. To test the effect of PPARgamma agonist PGZ in vivo, hepatic fibrosis was evaluated in Balb/C or C57BL6/J mice treated with CCl4 (three times a week for 4 weeks; or corn oil for controls), and fed a normal or a PGZ-supplemented diet (0.01% wt/wt). PGZ treatment was associated with increased serum adiponectin concentrations but did not decrease the severity of hepatic fibrosis induced by CCl4.
PMID: 17143554