title: Syndecan-2 and decorin: proteoglycans with a difference--implications in keloid pathogenesis.
abstract: BACKGROUND
  Growth factors and cytokines involved in the wound healing process seem to be immobilized at the cell surface and extracellular matrix via binding with proteoglycans, making them important modulators of cell dynamics. Our aim was to investigate the expression of two proteoglycans, namely syndecan-2 and decorin, and to elucidate their role in the pathogenesis of an aberrant wound healing process leading to keloid scar.
  
  
  METHODS
  Intrinsic expression of syndecan-2, fibroblast growth factor (FGF)-2, and decorin in keloid tissue was investigated using Western blotting and immunohistochemistry. Normal and keloid fibroblasts were treated with serum to see the effects of serum growth factors on the expression of syndecan-2 and decorin. The role of epithelial-mesenchymal interactions in modulating syndecan-2, FGF-2, and decorin expression was investigated using an established two-chamber serum-free coculture model. Finally, the antifibrotic effect of decorin was investigated by studying its effect on the expression of extracellular matrix components.
  
  
  RESULTS
  Syndecan-2 and FGF-2 were upregulated in keloid tissue; decorin was downregulated. Normal and keloid fibroblasts treated with serum led to increase in syndecan-2 and decrease in decorin expression. Under coculture conditions, syndecan-2 was shed in the conditioned media. FGF-2 was also upregulated under coculture conditions and, when added to fibroblast monocultures, increased shedding of syndecan-2. Decorin levels were upregulated under coculture conditions only in normal cocultures. Decorin was also able to decrease extracellular matrix proteins, highlighting its importance as an antifibrotic agent.
  
  
  CONCLUSIONS
  Syndecan-2 and FGF-2 are not only overexpressed in keloid tissues but may interact with each other resulting in the shedding of syndecan-2, which in turn might activate a whole cascade of events responsible for a keloidic phenotype. In addition, decorin had an antifibrotic effect and could well be used as a potential therapeutic agent for keloids.
authors.affiliation: Department of Surgery, National University of Singapore, Singapore.
authors.forename: Anandaroop
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Man Yi
authors.initials: MY
authors.lastname: Wong
authors.forename: Sui Y
authors.initials: SY
authors.lastname: Chan
authors.forename: Dang V
authors.initials: DV
authors.lastname: Do
authors.forename: Audrey
authors.initials: A
authors.lastname: Khoo
authors.forename: Chee T
authors.initials: CT
authors.lastname: Ong
authors.forename: Han H
authors.initials: HH
authors.lastname: Cheong
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; D018920:Coculture Techniques; D058575:Decorin; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007627:Keloid / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D010641:Phenotype; D011509:Proteoglycans / Q000378:metabolism*; D053669:Syndecan-2 / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D016222:Fibroblast Growth Factor 2; D053669:Syndecan-2