Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists attenuate the profibrotic response induced by TGF-beta1 in renal interstitial fibroblasts.
BACKGROUND
Studies have shown that peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists could ameliorate renal fibrotic lesions in both diabetic nephropathy and nondiabetic chronic kidney diseases. In order to elucidate the antifibrotic mechanism of PPAR-gamma agonists, we investigated the effects of PPAR-gamma activation on TGF-beta1-induced renal interstitial fibroblasts.


METHODS
In rat renal interstitial fibroblasts (NRK/49F), the mRNA expression of TGF-beta1-induced alpha-smooth muscle actin (alpha-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-beta1 enhanced CTGF, FN and Col III mRNA expression in a dose- and time-dependent manner. alpha-SMA, CTGF, FN and Col III mRNA and FN protein expression in 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2)-troglitazone- and ciglitazone-pretreated groups, respectively, were significantly decreased compared with the TGF-beta1-stimulated group. TGF-beta1 (5 ng/mL) enhanced p-Smad2/3 protein expression in a time-dependent manner. Compared with the TGF-beta1-stimulated group, p-Smad2/3 protein induced by TGF-beta1 in PPAR-gamma agonists-pretreated groups significantly decreased with no statistical difference amongst the three pretreated groups.


CONCLUSIONS
PPAR-gamma agonists could inhibit TGF-beta1-induced renal fibroblast activation, CTGF expression and ECM synthesis through abrogating the TGF-beta1/Smads signaling pathway.
Wang
Weiming
W
Department of Nephrology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Liu
Feng
F
Chen
Nan
N
D000199:Actins / Q000378:metabolism*; D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation; D005347:Fibroblasts / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D005355:Fibrosis; D007668:Kidney / Q000378:metabolism*; D008954:Models, Biological; D009130:Muscle, Smooth / Q000378:metabolism*; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D000199:Actins; D005353:Fibronectins; D047495:PPAR gamma; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1