title: WNT3A induces a contractile and secretory phenotype in cultured vascular smooth muscle cells that is associated with increased gap junction communication.
abstract: Evidence suggests a role for Wnt signaling in vascular wound repair and remodeling events. Despite this, very little is known about the effect of Wnt ligands on the structure and function of vascular cells. In this study, we treated vascular smooth muscle cells with 250 ng/ml of recombinant Wnt3a for 72 h and observed changes in the cell phenotype. Our data suggest Wnt3a completely alters the phenotype of vascular smooth muscle cells. The Wnt3a-treated cells appeared larger and had increased formation of stress fibers. These cells also had increased expression of the smooth muscle contractile proteins, calponin and smooth muscle α-actin, and contracted a collagen lattice faster than control cells. The Wnt3a-treated smooth muscle cells displayed increased extracellular matrix synthesis, as measured by collagen I and III mRNA expression, along with increased expression of MMP2 and MMP9, but decreased TIMP2 levels. The Wnt3a-induced change in cell phenotype was associated with increased expression of the gap junction protein connexin 43. Consistent with this, Wnt3a-treated smooth muscle cells displayed enhanced intercellular communication, as measured by the scrape-loading dye transfer technique. The canonical Wnt antagonist, dickkopf-related protein 1, completely reversed the contractile protein and connexin 43 expression seen in the Wnt3a-treated cells, suggesting these changes were dependent on canonical Wnt signaling. Collectively, this data suggest Wnt3a promotes a contractile and secretory phenotype in vascular smooth muscle cells that is associated with increased gap junction communication.
authors: Department of Pathology and Laboratory Medicine, James Hogg Research Centre, Institute for Heart+Lung Health, University of British Columbia, Vancouver, British Columbia, Canada.
authors: Jon M
authors: JM
authors: Carthy
authors: Zongshu
authors: Z
authors: Luo
authors: Bruce M
authors: BM
authors: McManus
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002450:Cell Communication; D002460:Cell Line; D049109:Cell Proliferation; D017629:Gap Junctions / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D060509:Wnt3A Protein / Q000502:physiology*
chemical_list: D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse