PPARγ agonist and angiotensin II receptor antagonist ameliorate renal tubulointerstitial fibrosis

Jee Young Han, Ye Ji Kim, Lucia Kim, Suk Jin Choi, In Suh Park, Joon Mee Kim, Young Chae Chu, Dae Ryong Cha

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The peroxisome proliferator activated receptor (PPAR)γ agonist is used as antidiabetic agent with antihyperglycemic and antihyperinsulinemic actions. Beyond these actions, antifibrotic effects have been reported. We examined antifibrotic effects of PPARγ 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 pSmad2 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-β1 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-β/Smad2 in the treated groups, PAI-1 and TGF-β are likely linked to the decreased renal tubulointerstitial fibrosis. According to these results, the PPARγ agonist might be used in the treatment of renal fibrotic disease.

Original languageEnglish
Pages (from-to)35-41
Number of pages7
JournalJournal of Korean medical science
Volume25
Issue number1
DOIs
Publication statusPublished - 2010 Jan

Keywords

  • Angiotensin
  • Fibrosis
  • PPAR gamma
  • Plasminogen activator inhibitor 1
  • Receptors
  • Transforming growth factor beta

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Han, J. Y., Kim, Y. J., Kim, L., Choi, S. J., Park, I. S., Kim, J. M., Chu, Y. C., & Cha, D. R. (2010). PPARγ agonist and angiotensin II receptor antagonist ameliorate renal tubulointerstitial fibrosis. Journal of Korean medical science, 25(1), 35-41. https://doi.org/10.3346/jkms.2010.25.1.35