Peroxisome Proliferator-Activated Receptor- [Formula: see text] (PPAR- [Formula: see text]) Agonists Attenuate the Profibrotic Response Induced by TGF- [Formula: see text] 1 in Renal Interstitial Fibroblasts

Background. Studies have shown that peroxisome proliferator-activated receptor- [Formula: see text] (PPAR- [Formula: see text]) agonists could ameliorate renal fibrotic lesions in both diabetic nephropathy and nondiabetic chronic kidney diseases. In order to elucidate the antifibrotic mechanism of P...

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Detalles Bibliográficos
Autores principales: Wang, Weiming, Liu, Feng, Chen, Nan
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2007
Materias:
Research Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2220083/
https://www.ncbi.nlm.nih.gov/pubmed/18274641
http://dx.doi.org/10.1155/2007/62641
Descripción
Sumario:Background. Studies have shown that peroxisome proliferator-activated receptor- [Formula: see text] (PPAR- [Formula: see text]) agonists could ameliorate renal fibrotic lesions in both diabetic nephropathy and nondiabetic chronic kidney diseases. In order to elucidate the antifibrotic mechanism of PPAR- [Formula: see text] agonists, we investigated the effects of PPAR- [Formula: see text] activation on TGF- [Formula: see text] 1-induced renal interstitial fibroblasts. Methods. In rat renal interstitial fibroblasts (NRK/49F), the mRNA expression of TGF- [Formula: see text] 1-induced [Formula: see text]-smooth muscle actin ([Formula: see text]-SMA), connective tissue growth factor (CTGF), fibronectin (FN) and collagen type III (Col III) were observed by reverse transcriptase-polymerase chain reaction (RT-PCR). The protein expressions of FN and Smads were observed by Western blot. Results. In NRK/49F, TGF- [Formula: see text] 1 enhanced CTGF, FN and Col III mRNA expression in a dose- and time-dependent manner. [Formula: see text]-SMA, CTGF, FN and Col III mRNA and FN protein expression in 15-deoxy- [Formula: see text]-prostaglandin J2 (15d-PGJ2)-troglitazone- and ciglitazone-pretreated groups, respectively, were significantly decreased compared with the TGF- [Formula: see text] 1-stimulated group. TGF- [Formula: see text] 1 (5 ng/mL) enhanced p-Smad2/3 protein expression in a time-dependent manner. Compared with the TGF- [Formula: see text] 1-stimulated group, p-Smad2/3 protein induced by TGF- [Formula: see text] 1 in PPAR- [Formula: see text] agonists-pretreated groups significantly decreased with no statistical difference amongst the three pretreated groups. Conclusion. PPAR- [Formula: see text] agonists could inhibit TGF- [Formula: see text] 1-induced renal fibroblast activation, CTGF expression and ECM synthesis through abrogating the TGF- [Formula: see text] 1/Smads signaling pathway.

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