Activation of peroxisome proliferator-activated receptor-γ inhibits transforming growth factor-β1 induction of connective tissue growth factor and extracellular matrix in hypertrophic scar fibroblasts in vitro

被引：0
作者：
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
Wei-Yang Gao
机构：
[1] The 2nd Affiliated Hospital of Wenzhou Medical College,Department of Hand and Plastic Surgery
[2] Shanghai Jiaotong University,Department of Orthopaedic Surgery, Shanghai Sixth People’s Hospital, School of Medicine
[3] The First Affiliated Hospital of Wenzhou Medical College,Department of Infection and Liver Diseases
[4] Fourth Military Medical University,Institute of Plastic Surgery, Xijing Hospital
来源：
Archives of Dermatological Research | 2009年 / 301卷
关键词：
Peroxisome proliferator-activated receptor-γ; Transforming growth factor β1; Connective tissue growth factor; Hypertrophic scar;
D O I：
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学科分类号：
摘要：
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.
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页码：515 / 522
页数：7
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