title: c-Ski promotes skin fibroblast proliferation but decreases type I collagen: implications for wound healing and scar formation.
abstract: 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-beta1/Smad3 in epithelial cells and as a complicated regulator of embryo fibroblast proliferation, may play such a role through modulation of skin fibroblast function.
  
  
  OBJECTIVE
  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.
authors.affiliation: Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing, China. lxflying@yahoo.com.cn
authors.forename: X
authors.initials: X
authors.lastname: Liu
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: X-Y
authors.initials: XY
authors.lastname: Chen
authors.forename: Y-G
authors.initials: YG
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002921:Cicatrix / Q000378:metabolism / Q000473:pathology*; D024042:Collagen Type I / Q000096:biosynthesis* / Q000235:genetics; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism / Q000473:pathology*; D051900:Smad3 Protein / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C525545:Ski protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat