Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist inhibits transforming growth factor-beta1 and matrix production in human dermal fibroblasts.

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

Department of Hand and Plastic Surgery, The second Affiliated Hospital of Wenzhou Medical College, Xueyuan West Road 109#, Wenzhou 325027, Zhejiang Province, PR China.

Journal of plastic, reconstructive & aesthetic surgery : JPRAS 2010 Jul

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Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are increasingly used in patients with diabetes, and some studies have suggested a beneficial effect on organ fibrosis, but their effects on dermal cell growth and extracellular matrix (ECM) turnover are unknown. To investigate the effect of the PPAR-gamma agonist troglitazone on cell growth and matrix production in human dermal fibroblasts (HDF), HDF were cultured and grown in a different concentration of troglitazone. PPAR-gamma expression and matrix production were measured in HDF in the presence of troglitazone. The mRNA expressions of TGF-beta1, collagen I (Col I) and fibronectin (FN) were determined by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The protein of transforming growth factor-beta1 (TGF-beta1) was determined by enzyme-linked immunosorbent assay (ELISA) and proteins of Col I and FN were determined by Western blotting. The mRNA expression of TGF-beta1, Col I and FN were significantly decreased in HDF in 15-30 micromol l(-1) troglitazone compared to the control group with Dulbecco's modified Eagle's medium (P<0.01). An obvious decrease of TGF-beta1 protein was found in troglitazone-treated groups as compared to the control group (P<0.05). Exposure of HDF to troglitazone reduced col I secretion (P<0.05), and fibronectin secretion (P<0.05). This study suggests that PPAR-gamma agonist will provide a novel approach with therapeutic potential in dermal fibrosis, such as hypertrophic scar, keloid and so on. Crown Copyright 2009. Published by Elsevier Ltd. All rights reserved.

Citation

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. Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist inhibits transforming growth factor-beta1 and matrix production in human dermal fibroblasts. Journal of plastic, reconstructive & aesthetic surgery : JPRAS. 2010 Jul;63(7):1209-16