- Title
- Versican V1 overexpression induces a myofibroblast-like phenotype in cultured fibroblasts
- Creator
- Carthy, Jon M.; Meredith, Anna J.; Boroomand, Seti; Abraham, Thomas; Luo, Zongshu; Knight, Darryl; McManus, Bruce M.
- Relation
- PLoS One Vol. 10, Issue 7
- Publisher Link
- http://dx.doi.org/10.1371/journal.pone.0133056
- Publisher
- Public Library of Science (PLOS)
- Resource Type
- journal article
- Date
- 2015
- Description
- 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 a-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.
- Subject
- Versican; injury; cell function; cDNA; fibroblasts
- Identifier
- http://hdl.handle.net/1959.13/1332917
- Identifier
- uon:26972
- Identifier
- ISSN:1932-6203
- Rights
- © 2015 Carthy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
- Language
- eng
- Full Text
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