title: Collagen triple helix repeat containing-1 inhibits  transforming growth factor-b1-induced collagen type I  expression in keloid.
abstract: BACKGROUND
  Keloids are benign skin tumours occurring during wound healing in genetically predisposed patients. There is evidence that transforming growth factor (TGF)-b is involved in keloid formation. Collagen triple helix repeat containing- 1 (Cthrc1) was identified as a novel gene expressed in the adventitia and neointima on arterial injury. It is indicated to be a cell type-specific inhibitor of TGF-b, which functionally increases cell migration while reducing collagen type I and III deposition. However, to our knowledge expression and regulatory mechanisms of Cthrc1 and TGF-b1 in keloid and normal skin have not been studied before.
  
  
  OBJECTIVE
  Cthrc1 gene regulation and potential role in keloid formation were determined, and its correlation with TGF-b1 involved in keloid pathogenesis was examined in human fibroblasts of keloids and normal skin.
  
  
  METHODS
  The expression of Cthrc1 and TGF-b1 was investigated in fibroblasts of keloid and normal skin. Collagen type I expression and collagen synthesis in keloid fibroblasts induced by TGF-b1 were examined. Then, recombinant Cthrc1 was applied to assess its correlation with TGF-b1.
  
  
  RESULTS
  Increased TGF-b1 and Cthrc1 expression was examined in keloid compared with normal skin. Cthrc1 expression increased in a concentration-dependent manner induced by TGF-b1 in keloid fibroblasts. TGF-b1 stimulated collagen type I expression and collagen synthesis in keloid fibroblasts, which can be reversed by recombinant Cthrc1.
  
  
  CONCLUSIONS
  TGF-b1 was upregulated in keloid fibroblasts and recombinant Cthrc1 inhibited TGF-b1-stimulated collagen type I synthesis, which suggests that Cthrc1 may be a potential therapeutic option for keloids.
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Cao
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: Y
authors.initials: Y
authors.lastname: Yang
authors.forename: X
authors.initials: X
authors.lastname: Xiao
authors.forename: Z
authors.initials: Z
authors.lastname: Wu
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Tu
authors.forename: H
authors.initials: H
authors.lastname: Chen
mesh_terms: D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007627:Keloid / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: C502426:CTHRC1 protein, human; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D053773:Transforming Growth Factor beta1