Guo-You Zhang, Tao Cheng, Ming-Hua Zheng, Cheng-Gang Yi, Hua Pan, Zhi-Jie Li, Xing-Long Chen, Qing Yu, Liang-Fu Jiang, Fei-Ya Zhou, Xiao-Yang Li, Jing-Quan Yang, Ting-Gang Chu, and Wei-Yang Gao
Peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-γ ligands in the presence of transforming growth factor-β1 (TGF-β1). In growth-arrested HSFs, a PPAR-γ natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFβ1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-γ (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-β1/Smad pathway. These results suggest that in TGFβ1-stimulated HSFs, PPAR-γ ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-γ and Smad may be involved in the inhibitory effects of PPAR-γ ligands. [ABSTRACT FROM AUTHOR]