title: The role of hepatocyte growth factor/c-Met system in keloid pathogenesis.
abstract: BACKGROUND
  Keloid scar is a fibroproliferative disorder characterized by increased deposition of extracellular matrix components. Hepatocyte growth factor (HGF), also known as the "scatter factor," and its receptor, a product of the Met oncogene, play multiple roles in regulating cell behavior. However, the role of this system in pathogenic fibrosis is still unclear. Our aim was to investigate and to clarify the role of HGF and its receptor c-Met in pathogenesis of keloid scars.
  
  
  METHODS
  This study investigated the expression profile of HGF and c-Met in keloid and normal skin tissue. In addition, the role of normal and keloid keratinocytes in modulating the expression of fibroblast HGF (epithelial-mesenchymal interactions) was examined using a two-chamber serum-free coculture model. The effect of serum stimulation on fibroblast expression of HGF and c-Met was also studied.
  
  
  RESULTS
  Increased levels of HGF and c-Met were observed in tissue extracts obtained from keloid tissue. Increased levels of HGF and c-Met localization were observed in the basal epidermis and in the dermis of keloid tissue compared with normal skin. Serum stimulation seemed to upregulate the expression of both HGF and c-Met in fibroblasts. Finally, coculture of keloid keratinocytes with keloid fibroblasts upregulated levels of both HGF and c-Met in keratinocyte cell lysates and conditioned media obtained from fibroblast culture.
  
  
  CONCLUSIONS
  These findings emphasize the importance of the HGF/c-Met system in keloid biology and pathogenesis and suggest a possible target for therapeutic intervention in the prevention and treatment of keloids.
authors.affiliation: Department of Surgery, National University of Singapore, Singapore.
authors.forename: Anandaroop
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Spencer
authors.initials: S
authors.lastname: Fan
authors.forename: Vinh D
authors.initials: VD
authors.lastname: Dang
authors.forename: Audrey
authors.initials: A
authors.lastname: Khoo
authors.forename: Chee T
authors.initials: CT
authors.lastname: Ong
authors.forename: Ivor J
authors.initials: IJ
authors.lastname: Lim
authors.forename: Thang T
authors.initials: TT
authors.lastname: Phan
mesh_terms: D000704:Analysis of Variance; D015153:Blotting, Western; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D007627:Keloid / Q000378:metabolism* / Q000473:pathology; D015603:Keratinocytes / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met