KMID : 1141520170320010115
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Endocrinology and Metabolism 2017 Volume.32 No. 1 p.115 ~ p.123
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Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor ¥ã Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
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Bae Kwi-Hyun
Seo Jung-Beom Jung Yun-A Seo Hye-Young Kang Sun-Hee Jeon Hui-Jeon Lee Jae-Man Lee Sung-Woo Kim Jung-Guk Lee In-Kyu Jung Gwon-Soo Park Keun-Gyu
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Abstract
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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 ¥ã (PPAR¥ã) 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 PPAR¥ã 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, ¥á-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-¥â/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.
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KEYWORD
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Renal tubulointerstitial fibrosis, Lobeglitazone, Transforming growth factor beta, Unilateral ureteral obstruction
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