Recombinant human decorin inhibits cell proliferation and downregulates TGF-β1 production in keloid fibroblasts

Keloids remain a major problem for patients who have suffered deep injuries. The pathophysiology underlying keloid formation may be driven by the biological activity of transforming growth factor betal (TGF-beta 1). Decorin is a human proteoglycan that inactivates the effect of TGF-beta 1 and therefore displays a beneficial effect of antifibrosis in various tissues, such as kidney, muscle, and lung. Keloids are fibroproliferative disorders of the dermis that occur following wounding. This study investigated the effects of decorin on cell proliferation, TGF-beta 1 production, and collagen synthesis in keloid fibroblasts. Fibroblasts were extracted from explants of operative specimens obtained from keloid tissue and cultured in vitro with serial, diluted decorin concentrations (10, 50, 100, 200 nM) for 48 hours. The cell proliferation rates were measured by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide] colorimetric determination, and cell cycle distributions were analyzed with flow cytometry. Low-molecular-weight apoptotic DNA and TGF-beta 1 levels in supernatants were measured by enzyme-linked immunosorbent assay. Radioimmunoassay was used to detect the contents of type I and type III collagen amino-terminal propeptide (PINP, PIIINP) in supernatants. Fibroblast proliferation was significantly (P < 0.05) inhibited by decorin at all concentrations (12, 24, and 48 hours) and was dose-dependent. Decorin inhibited fibroblast proliferation by inducing cell growth arrest but not apoptosis. TGF-beta 1 and PINP levels were significantly (P < 0.05) lower in fibroblasts treated with 10, 50, 100, and 200 nM of decorin for 48 hours compared with fibroblasts not treated with decorin. There was no significant difference in PIIINP concentration between the decorin-treated group and the control group. The PINP/PIIINP ratios were significantly lower in fibroblasts treated with decorin (P < 0.05) compared to the control group. These results suggest that decorin has a down-regulatory effect on cell proliferation, TGF-beta 1 production, and collagen synthesis in keloid fibroblasts. Improved understanding of such regulatory mechanisms may eventually be of therapeutic significance in the control of keloid.