Versican V1 overexpression induces a myofibroblast-like phenotype in cultured fibroblasts

Jon M. Carthy, Anna J. Meredith, Seti Boroomand, Thomas Abraham, Zongshu Luo, Darryl Knight, Bruce M. McManus

Research output: Contribution to journalArticle

12 Scopus citations

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. Methods and 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.

Original languageEnglish (US)
Article numbere0133056
JournalPloS one
Volume10
Issue number7
DOIs
StatePublished - Jul 15 2015

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Carthy, J. M., Meredith, A. J., Boroomand, S., Abraham, T., Luo, Z., Knight, D., & McManus, B. M. (2015). Versican V1 overexpression induces a myofibroblast-like phenotype in cultured fibroblasts. PloS one, 10(7), [e0133056]. https://doi.org/10.1371/journal.pone.0133056