Versican V1 Overexpression Induces a Myofibroblast-Like Phenotype in Cultured Fibroblasts

• Published in: PloS one Vol. 10; no. 7; p. e0133056
• Main Authors: Carthy, Jon M, Meredith, Anna J, Boroomand, Seti, Abraham, Thomas, Luo, Zongshu, Knight, Darryl, McManus, Bruce M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 15.07.2015; Public Library of Science (PLoS)
• Subjects: Actin; Actins - genetics; Actins - metabolism; Animals; Apoptosis; Bone morphogenetic proteins; Cadherin; Cadherins; Cadherins - genetics; Cadherins - metabolism; Cell adhesion; Cell adhesion & migration; Cell Differentiation; Cell Line; Cloning; Collagen; Collagen (type III); Collagen Type III - genetics; Collagen Type III - metabolism; Disease; Experiments; Extracellular matrix; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Focal Adhesion Kinase 1 - genetics; Focal Adhesion Kinase 1 - metabolism; Gene expression; Gene Expression Regulation; Genetic aspects; Genotype & phenotype; Growth factors; Heart; Humans; Integrin beta1 - genetics; Integrin beta1 - metabolism; Integrins; Kinases; Laboratories; Medicine; Mice; Mucopolysaccharides; Muscle proteins; Muscles; Myofibroblasts - cytology; Myofibroblasts - metabolism; N-Cadherin; Pathology; Phenotype; Phosphorylation; Proteins; RNA; Signal Transduction; Signaling; Smad2 protein; Smad2 Protein - genetics; Smad2 Protein - metabolism; Smooth muscle; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta - metabolism; Transforming growth factors; Transgenes; Versican; Versicans - genetics; Versicans - metabolism; Wound healing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0133056

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. 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. Collectively, these data indicate versican expression induces a myofibroblast-like phenotype in cultured fibroblasts.