title: Versican V1 Overexpression Induces a Myofibroblast-Like Phenotype in Cultured Fibroblasts.
abstract: BACKGROUND
  Versican, a chondroitin sulphate proteoglycan, is one of the key components of the provisional extracellular matrix expressed after injury. The current study evaluated the hypothesis that a versican-rich matrix alters the phenotype of cultured fibroblasts.
  
  
  RESULTS
  The full-length cDNA for the V1 isoform of human versican was cloned and the recombinant proteoglycan was expressed in murine fibroblasts. Versican expression induced a marked change in fibroblast phenotype. Functionally, the versican-expressing fibroblasts proliferated faster and displayed enhanced cell adhesion, but migrated slower than control cells. These changes in cell function were associated with greater N-cadherin and integrin β1 expression, along with increased FAK phosphorylation. The versican-expressing fibroblasts also displayed expression of smooth muscle α-actin, a marker of myofibroblast differentiation. Consistent with this observation, the versican fibroblasts displayed increased synthetic activity, as measured by collagen III mRNA expression, as well as a greater capacity to contract a collagen lattice. These changes appear to be mediated, at least in part, by an increase in active TGF-β signaling in the versican expressing fibroblasts, and this was measured by phosphorylation and nuclear accumulation of SMAD2.
  
  
  CONCLUSIONS
  Collectively, these data indicate versican expression induces a myofibroblast-like phenotype in cultured fibroblasts.
authors.affiliation: UBC James Hogg Research Centre, Institute for Heart + Lung Health, Department of Pathology and Laboratory Medicine, University of British Columbia - Providence Health Care, Vancouver, British Columbia, Canada.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Carthy
authors.affiliation: UBC James Hogg Research Centre, Institute for Heart + Lung Health, Department of Pathology and Laboratory Medicine, University of British Columbia - Providence Health Care, Vancouver, British Columbia, Canada.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Meredith
authors.affiliation: UBC James Hogg Research Centre, Institute for Heart + Lung Health, Department of Pathology and Laboratory Medicine, University of British Columbia - Providence Health Care, Vancouver, British Columbia, Canada.
authors.forename: Seti
authors.initials: S
authors.lastname: Boroomand
authors.affiliation: UBC James Hogg Research Centre, Institute for Heart + Lung Health, Department of Pathology and Laboratory Medicine, University of British Columbia - Providence Health Care, Vancouver, British Columbia, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Abraham
authors.affiliation: UBC James Hogg Research Centre, Institute for Heart + Lung Health, Department of Pathology and Laboratory Medicine, University of British Columbia - Providence Health Care, Vancouver, British Columbia, Canada.
authors.forename: Zongshu
authors.initials: Z
authors.lastname: Luo
authors.affiliation: UBC James Hogg Research Centre, Institute for Heart + Lung Health, Department of Pathology and Laboratory Medicine, University of British Columbia - Providence Health Care, Vancouver, British Columbia, Canada.
authors.forename: Darryl
authors.initials: D
authors.lastname: Knight
authors.affiliation: UBC James Hogg Research Centre, Institute for Heart + Lung Health, Department of Pathology and Laboratory Medicine, University of British Columbia - Providence Health Care, Vancouver, British Columbia, Canada.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: McManus
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D058628:Myofibroblasts / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D015398:Signal Transduction; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D019076:Transgenes; D053675:Versicans / Q000235:genetics* / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D024061:Collagen Type III; D019012:Integrin beta1; D051899:Smad2 Protein; D016212:Transforming Growth Factor beta; C544013:alpha-smooth muscle actin, mouse; D053675:Versicans; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse