Premium
c‐Ski promotes skin fibroblast proliferation but decreases type I collagen: implications for wound healing and scar formation
Author(s) -
Liu X.,
Li P.,
Chen X.Y.,
Zhou Y.G.
Publication year - 2010
Publication title -
clinical and experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.587
H-Index - 78
eISSN - 1365-2230
pISSN - 0307-6938
DOI - 10.1111/j.1365-2230.2009.03606.x
Subject(s) - fibroblast , wound healing , myofibroblast , cell growth , microbiology and biotechnology , blot , type i collagen , transfection , chemistry , cell cycle , biology , cell , cell culture , immunology , pathology , fibrosis , endocrinology , medicine , biochemistry , genetics , gene
Summary Background. Accelerating wound healing is always accompanied by excessive scar formation. The focus in chronic wounds has been promoting the proliferation of tissue repair cells while decreasing collagen deposition. Smad3 null mice display more rapid wound closure and reduced scar formation. We hypothesized that c‐Ski, acting as a co‐repressor of transforming growth factor‐β1/Smad3 in epithelial cells and as a complicated regulator of embryo fibroblast proliferation, may play such a role through modulation of skin fibroblast function. Aim. To investigate the effect of c‐Ski on skin fibroblast proliferation, cell‐cycle progression, type I collagen secretion and myofibroblast differentiation. The potential involvement of Smad3 was also investigated. Methods. Cultured rat skin fibroblasts were used. Immunocytochemistry and reverse transcription (RT)‐PCR was used to examine the localization and expression of c‐Ski. Plasmid transfection technology was used to produce c‐Ski or/and Smad3 overexpression. Cell proliferation was analysed by 5‐bromo‐2‐deoxyuridine incorporation; cell cycle by fluorescence‐activated cell sorting; type I collagen expression by immunocytochemistry, RT‐PCR and western blotting; and myofibroblast differentiation by western blotting. Results. c‐Ski was expressed in cultured skin fibroblasts. Overexpression of c‐Ski was able to promote skin fibroblast proliferation and accelerate cell‐cycle progression through inhibiting Smad3 activity. It also decreased type I collagen protein and mRNA expression through inhibiting Smad3 activity. It did not affect fibroblast–myofibroblast differentiation. Conclusions. Because of the important role of fibroblast proliferation and collagen secretion in tissue repair and scar formation, we speculate that c‐Ski may be a new candidate molecule for accelerating wound healing and decreasing scar formation.