Lobeglitazone, a Novel Peroxisome Proliferator-Activated Receptor γ Agonist, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
Endocrinology and Metabolism
; : 115-123, 2017.
Artículo
en Inglés
| WPRIM (Pacífico Occidental)
| ID: wpr-64568
Biblioteca responsable:
WPRO
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.
Texto completo:
Disponible
Base de datos:
WPRIM (Pacífico Occidental)
Asunto principal:
Fosforilación
/
Atrofia
/
Uréter
/
Obstrucción Ureteral
/
Técnicas In Vitro
/
Fibrosis
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Factores de Crecimiento Transformadores
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Regulación hacia Arriba
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Western Blotting
/
Reacción en Cadena de la Polimerasa
Límite:
Animales
Idioma:
Inglés
Revista:
Endocrinology and Metabolism
Año:
2017
Tipo del documento:
Artículo