Recombinant human decorin inhibits cell proliferation and downregulates TGF-beta1 production in hypertrophic scar fibroblasts.
Hypertrophic scarring remains a major problem for patients who have suffered deep burns. The pathophysiology underlying hypertrophic scar formation may be driven by the biological activity of transforming growth factor beta1 (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. Hypertrophic scarring is a fibroproliferative disorder of the dermis that occurs following wounding. This study investigated the effects of decorin on cell proliferation, TGF-beta(1) production, and collagen synthesis in hypertrophic scar fibroblasts. The cell proliferation rates, cell cycle distribution, low-molecular-weight apoptotic DNA and TGF-beta(1) levels, and contents of type I and type III collagen amino-terminal propeptide (PINP, PIIINP) in supernatants were assessed. Fibroblast proliferation was significantly (P<0.05) inhibited by decorin, and this effect was dose-dependent. The fibroblast population became stationary at decorin concentrations of 100 and 200 nM. 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, 200 nM of decorin compared with fibroblasts without decorin addition. However, there was no significant difference in PIIINP concentration between the decorin-treated group and the control group. These results suggest that decorin has a down-regulatory effect on cell proliferation, TGF-beta(1) production, and collagen synthesis in hypertrophic scar fibroblasts. Improved understanding of such a regulatory mechanisms may eventually be of therapeutic significance in the control of hypertrophic scarring.
Zhang
Zhi
Z
Department of Burn and Plastic Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou 510220, PR China. zhangzhicc48@163.com
Li
Xiao-Jian
XJ
Liu
Yan
Y
Zhang
Xiong
X
Li
Ye-Yang
YY
Xu
Wei-Shi
WS
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017439:Cicatrix, Hypertrophic / Q000378:metabolism* / Q000473:pathology; D024042:Collagen Type I / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D058575:Decorin; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D011509:Proteoglycans / Q000494:pharmacology*; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D024042:Collagen Type I; D024043:Collagen Type II; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D011994:Recombinant Proteins; D053773:Transforming Growth Factor beta1