Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice.
10.3803/EnM.2017.32.1.115
- Author:
Kwi Hyun BAE
1
;
Jung Beom SEO
;
Yun A JUNG
;
Hye Young SEO
;
Sun Hee KANG
;
Hui Jeon JEON
;
Jae Man LEE
;
Sungwoo LEE
;
Jung Guk KIM
;
In Kyu LEE
;
Gwon Soo JUNG
;
Keun Gyu PARK
Author Information
1. Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea. kpark@knu.ac.kr mine9240@naver.com
- Publication Type:Original Article
- Keywords:
Renal tubulointerstitial fibrosis;
Lobeglitazone;
Transforming growth factor beta;
Unilateral ureteral obstruction
- MeSH:
Actins;
Animals;
Atrophy;
Blotting, Western;
Collagen Type I;
Diabetic Nephropathies;
Fibroblasts;
Fibrosis*;
In Vitro Techniques;
Mesangial Cells;
Mice*;
Peroxisomes*;
Phosphorylation;
Plasminogen Activator Inhibitor 1;
Polymerase Chain Reaction;
Rats;
Renal Insufficiency, Chronic;
Reverse Transcription;
Transforming Growth Factor beta;
Transforming Growth Factors;
Up-Regulation;
Ureter*;
Ureteral Obstruction*
- From:Endocrinology and Metabolism
2017;32(1):115-123
- CountryRepublic of Korea
- Language:English
-
Abstract:
BACKGROUND: Renal tubulointerstitial fibrosis is a common feature of the final stage of nearly all cause types of chronic kidney disease. Although classic peroxisome proliferator-activated receptor γ (PPARγ) agonists have a protective effect on diabetic nephropathy, much less is known about their direct effects in renal fibrosis. This study aimed to investigate possible beneficial effects of lobeglitazone, a novel PPARγ agonist, on renal fibrosis in mice. METHODS: We examined the effects of lobeglitazone on renal tubulointerstitial fibrosis in unilateral ureteral obstruction (UUO) induced renal fibrosis mice. We further defined the role of lobeglitazone on transforming growth factor (TGF)-signaling pathways in renal tubulointerstitial fibrosis through in vivo and in vitro study. RESULTS: Through hematoxylin/eosin and sirius red staining, we observed that lobeglitazone effectively attenuates UUO-induced renal atrophy and fibrosis. Immunohistochemical analysis in conjunction with quantitative reverse transcription polymerase chain reaction and Western blot analysis revealed that lobeglitazone treatment inhibited UUO-induced upregulation of renal Smad-3 phosphorylation, α-smooth muscle actin, plasminogen activator inhibitor 1, and type 1 collagen. In vitro experiments with rat mesangial cells and NRK-49F renal fibroblast cells suggested that the effects of lobeglitazone on UUO-induced renal fibrosis are mediated by inhibition of the TGF-β/Smad signaling pathway. CONCLUSION: The present study demonstrates that lobeglitazone has a protective effect on UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of non-diabetic origin renal disease.
