Role of caveolin-1 in the pathogenesis of tissue fibrosis by keloid-derived fibroblasts in vitro

P>Background Recent studies have suggested that caveolin-1 (cav-1) plays an important role in the regulation of transforming growth factor (TGF)-beta 1 signalling and participates in the pathogenesis of tissue fibrosis. However, its effects on dermal fibrosis keloids are unknown. Objectives To investigate the effect of cav-1 in the pathogenesis of tissue fibrosis by keloid fibroblasts. Methods Keloid fibroblasts were cultured and exposed to different concentrations of cav-1 cell-permeable peptides (cav-1p) in the presence of TGF-beta 1. Keloid fibroblast phenotypes and protein production were analysed by real-time reverse transcriptase-polymerase chain reaction, Western blot, and multiplex enzyme-linked immunosorbent assay techniques. The effect of cav-1p on cell viability was evaluated by MTT assay. Results Cav-1 was markedly decreased in the keloid-derived fibroblasts. Moreover, cav-1p significantly reduced TGF-beta receptor type I levels and Smad2/3 phosphorylation in response to added TGF-beta 1. Additionally, TGF-beta 1 decreased cav-1 expression in human skin fibroblasts. Cav-1 was able to suppress TGF-beta 1-induced extracellular matrix production in cultured keloid fibroblasts through regulation of the mitogen-activated protein kinase pathway. Conclusions Cav-1 appears to participate in the pathogenesis of tissue fibrosis in keloid. Restoration of cav-1 function by treatment with a cell-permeable peptide corresponding to the cav-1 scaffolding domain may be a novel therapeutic approach in keloid.