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 language | English |
|---|---|
| Pages (from-to) | 35-41 |
| Number of pages | 7 |
| Journal | Journal of Korean Medical Science |
| Volume | 25 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2010 Jan 1 |
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Keywords
- Angiotensin
- Fibrosis
- Plasminogen activator inhibitor 1
- PPAR gamma
- Receptors
- Transforming growth factor beta
ASJC Scopus subject areas
- Medicine(all)
Cite this
PPARγ agonist and angiotensin II receptor antagonist ameliorate renal tubulointerstitial fibrosis. / Han, Jee Young; Kim, Ye Ji; Kim, Lucia; Choi, Suk Jin; Park, In Suh; Kim, Joon Mee; Chu, Young Chae; Cha, Dae-Ryong.
In: Journal of Korean Medical Science, Vol. 25, No. 1, 01.01.2010, p. 35-41.Research output: Contribution to journal › Article
}
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
PY - 2010/1/1
Y1 - 2010/1/1
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 - Plasminogen activator inhibitor 1
KW - PPAR gamma
KW - Receptors
KW - Transforming growth factor beta
UR - http://www.scopus.com/inward/record.url?scp=77949324227&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77949324227&partnerID=8YFLogxK
U2 - 10.3346/jkms.2010.25.1.35
DO - 10.3346/jkms.2010.25.1.35
M3 - Article
VL - 25
SP - 35
EP - 41
JO - Journal of Korean Medical Science
JF - Journal of Korean Medical Science
SN - 1011-8934
IS - 1
ER -