Peroxisome Proliferator-Activated Receptor-γ(PPAR-γ) Agonists Attenuate the Profibrotic Response Induced by TGF-β1 in Renal Interstitial Fibroblasts

Abstract

Background.Studies have shown that peroxisome proliferator-activated receptor-γ(PPAR-γ) agonists could ameliorate renal fibrotic lesions in both diabetic nephropathy and nondiabetic chronic kidney diseases. In order to elucidate the antifibrotic mechanism of PPAR-γagonists, we investigated the effects of PPAR-γactivation on TGF-β1-induced renal interstitial fibroblasts.Methods.In rat renal interstitial fibroblasts (NRK/49F), the mRNA expression of TGF-β1-inducedα-smooth muscle actin (α-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-β1 enhanced CTGF, FN and Col III mRNA expression in a dose- and time-dependent manner.α-SMA, CTGF, FN and Col III mRNA and FN protein expression in 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2)-troglitazone- and ciglitazone-pretreated groups, respectively, were significantly decreased compared with the TGF-β1-stimulated group. TGF-β1 (5 ng/mL) enhanced p-Smad2/3 protein expression in a time-dependent manner. Compared with the TGF-β1-stimulated group, p-Smad2/3 protein induced by TGF-β1 in PPAR-γagonists-pretreated groups significantly decreased with no statistical difference amongst the three pretreated groups.Conclusion.PPAR-γagonists could inhibit TGF-β1-induced renal fibroblast activation, CTGF expression and ECM synthesis through abrogating the TGF-β1/Smads signaling pathway.