PPARgamma agonist and angiotensin II receptor antagonist ameliorate renal tubulointerstitial fibrosis.
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.
Han
Jee-Young
JY
Department of Pathology, Inha University Hospital, Inha University Medical College, Incheon, Korea. jeeyhan@inha.ac.kr
Kim
Ye-Ji
YJ
Kim
Lucia
L
Choi
Suk-Jin
SJ
Park
In-Suh
IS
Kim
Joon-Mee
JM
Chu
Young Chae
YC
Cha
Dae-Ryong
DR
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047495:PPAR gamma / Q000819:agonists*; D000077205:Pioglitazone; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D014517:Ureteral Obstruction / Q000378:metabolism / Q000473:pathology
D057911:Angiotensin Receptor Antagonists; D000943:Antigens, Differentiation; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D017395:Plasminogen Activator Inhibitor 1; D051899:Smad2 Protein; D045162:Thiazolidinediones; D053773:Transforming Growth Factor beta1; C036763:monocyte-macrophage differentiation antigen; D000077205:Pioglitazone