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Troglitazone suppresses transforming growth factor‐ β 1‐induced collagen type I expression in keloid fibroblasts
Author(s) -
Zhang GY.,
Yi CG.,
Li X.,
Ma B.,
Li ZJ.,
Chen XL.,
Guo SZ.,
Gao WY.
Publication year - 2009
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/j.1365-2133.2008.08989.x
Subject(s) - troglitazone , keloid , transforming growth factor , type i collagen , fibroblast , peroxisome proliferator activated receptor , chemistry , endocrinology , medicine , fibrosis , viability assay , receptor , microbiology and biotechnology , cell , biology , biochemistry , pathology , in vitro
Summary Background Peroxisome proliferator‐activated receptor (PPAR)‐γ agonists are increasingly used in patients with diabetes and some studies have suggested a beneficial effect on organ fibrosis. However their effects on dermal fibrosis in keloids are unknown. Objective To investigate the effect of the PPAR‐γ agonist troglitazone on transforming growth factor (TGF)‐β1‐induced collagen type I expression in keloid fibroblasts. Methods Keloid fibroblasts were cultured and exposed to different concentrations of troglitazone in the presence of TGF‐β1. The mRNA expression of PPAR‐γ was determined by semiquantitative reverse transcriptase–polymerase chain reaction. The protein of PPAR‐γ, Smad2, Smad3, phoshpo‐Smad2/3 and collagen type I was determined by Western blotting and collagen synthesis was evaluated by measuring 3 H‐proline incorporation. The effect of troglitazone on cell viability was evaluated by the colorimetric conversion of 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide. Results PPAR‐γ was expressed at a moderate level in keloid fibroblasts. Troglitazone depressed TGF‐β1‐stimulated collagen type I expression and collagen synthesis in keloid fibroblasts in a concentration‐dependent manner. Moreover, troglitazone inhibited expression and phosphorylation of TGF‐β1‐induced Smad2/3. Cell viability was unaffected. These inhibitory effects of troglitazone were reversed by the PPAR‐γ‐specific antagonist GW9662. Conclusions Our data suggest that PPAR‐γ is present in keloid fibroblasts and PPAR‐γ activation inhibits TGF‐β1‐induced collagen type I expression at least in part by decreasing collagen synthesis. PPAR‐γ may be a promising therapeutic target for keloids.