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

9 Citations (Scopus)

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

Fingerprint

Versicans
Myofibroblasts
Fibroblasts
fibroblasts
Phenotype
phenotype
proteoglycans
Phosphorylation
Cadherins
collagen
phosphorylation
Collagen
chondroitin sulfate
Chondroitin Sulfate Proteoglycans
cadherins
integrins
Differentiation Antigens
Cell adhesion
cell adhesion
extracellular matrix

All Science Journal Classification (ASJC) codes

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

Cite this

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
Carthy, Jon M. ; Meredith, Anna J. ; Boroomand, Seti ; Abraham, Thomas ; Luo, Zongshu ; Knight, Darryl ; McManus, Bruce M. / Versican V1 overexpression induces a myofibroblast-like phenotype in cultured fibroblasts. In: PloS one. 2015 ; Vol. 10, No. 7.
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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.",
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Carthy, JM, Meredith, AJ, Boroomand, S, Abraham, T, Luo, Z, Knight, D & McManus, BM 2015, 'Versican V1 overexpression induces a myofibroblast-like phenotype in cultured fibroblasts', PloS one, vol. 10, no. 7, e0133056. https://doi.org/10.1371/journal.pone.0133056

Versican V1 overexpression induces a myofibroblast-like phenotype in cultured fibroblasts. / Carthy, Jon M.; Meredith, Anna J.; Boroomand, Seti; Abraham, Thomas; Luo, Zongshu; Knight, Darryl; McManus, Bruce M.

In: PloS one, Vol. 10, No. 7, e0133056, 15.07.2015.

Research output: Contribution to journalArticle

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AU - Carthy, Jon M.

AU - Meredith, Anna J.

AU - Boroomand, Seti

AU - Abraham, Thomas

AU - Luo, Zongshu

AU - Knight, Darryl

AU - McManus, Bruce M.

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Y1 - 2015/7/15

N2 - 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.

AB - 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.

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