TY - JOUR
T1 - PPARγ agonist and angiotensin II receptor antagonist ameliorate renal tubulointerstitial fibrosis
AU - Han, Jee Young
AU - Kim, Ye Ji
AU - Kim, Lucia
AU - Choi, Suk Jin
AU - Park, In Suh
AU - Kim, Joon Mee
AU - Chu, Young Chae
AU - Cha, Dae Ryong
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - Angiotensin
KW - Fibrosis
KW - PPAR gamma
KW - Plasminogen activator inhibitor 1
KW - Receptors
KW - Transforming growth factor beta
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U2 - 10.3346/jkms.2010.25.1.35
DO - 10.3346/jkms.2010.25.1.35
M3 - Article
C2 - 20052345
AN - SCOPUS:77949324227
VL - 25
SP - 35
EP - 41
JO - Journal of Korean Medical Science
JF - Journal of Korean Medical Science
SN - 1011-8934
IS - 1
ER -