JOURNAL ARTICLE

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists attenuate the profibrotic response induced by TGF-beta1 in renal interstitial fibroblasts

Weiming Wang, Feng Liu, Nan Chen
Mediators of Inflammation 2007, 2007: 62641
18274641

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.

CONCLUSION: PPAR-gamma agonists could inhibit TGF-beta1-induced renal fibroblast activation, CTGF expression and ECM synthesis through abrogating the TGF-beta1/Smads signaling pathway.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
18274641
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"