Versican V1 Overexpression Induces a Myofibroblast-Like Phenotype in Cultured Fibroblasts.
PLoS One
; 10(7): e0133056, 2015.
Article
en En
| MEDLINE
| ID: mdl-26176948
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 ß1 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-ß 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Regulación de la Expresión Génica
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Versicanos
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Miofibroblastos
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Fibroblastos
Límite:
Animals
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Humans
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2015
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Estados Unidos