The
peroxisome proliferator activated receptor (
PPAR)gamma agonist is used as
antidiabetic agent with
antihyperglycemic and antihyperinsulinemic actions. Beyond these actions, antifibrotic effects have been reported. We examined antifibrotic effects of
PPARgamma agonist and interaction with
angiotensin receptor antagonist in the unilateral
ureteral obstruction (UUO) model. After UUO, mice were divided to four groups: no treatment (CONT),
pioglitazone treatment, L158809 treatment, and L158809+
pioglitazone treatment. On day 14, CONT mice showed severe
fibrosis and all treated mice showed decreased
fibrosis. The immunohistochmistry of
PAI-1, F4/80 and p-Smad2 demonstrated that their expressions were increased in CONT group and decreased in the all treated groups compared to CONT.
PAI-1 and p-Smad2 determined from Western blotting, among treated groups, was decreased compared to CONT group. The expression of
TGF-beta1 from real time RT PCR showed markedly increased in the CONT group and decreased in all treated groups compared to CONT. These data suggest the
pioglitazone inhibited tubulointerstitial
fibrosis, however, the synergism between
pioglitazone and L158809 is not clear. Considering decreased expression of
PAI-1 and
TGF-beta/Smad2 in the treated groups,
PAI-1 and
TGF-beta are likely linked to the decreased renal tubulointerstitial
fibrosis. According to these results, the
PPARgamma agonist might be used in the treatment of renal fibrotic disease.