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Endocrinol Metab (Seoul). 2017 Mar;32(1):115-123. doi: 10.3803/EnM.2017.32.1.115. Epub 2017 Feb 28.

Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice.

Author information

1
Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea.
2
Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea.
3
Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea.
4
Department of Surgery, Keimyung University School of Medicine, Daegu, Korea.
5
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, Kyungpook National University School of Medicine, Daegu, Korea.
6
New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Korea.
7
Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea. mine9240@naver.com.
8
Leading-Edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea. kpark@knu.ac.kr.

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.

KEYWORDS:

Lobeglitazone; Renal tubulointerstitial fibrosis; Transforming growth factor beta; Unilateral ureteral obstruction

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

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