Wnt/β-catenin signaling regulates proteoglycan versican

The proteoglycan versican (VCN) is considered to be crucial in several key processes involved in vascular repair. The canonical Wnt-wingless/beta-catenin/T Cell Factor (TCF) signaling pathway regulates various biological events including early embryogenesis, neoplasia, and vascular remodeling. We investigated the role of beta-catenin/TCF signaling on regulation of VCN transcription. Upon activation of Writ signaling, TCF proteins interact with P-catenin and activate transcription of target genes. Cotransfection of beta-catenin and human VCN-Luciferase (VCN-Luc) constructs significantly enhanced promoter activity. Shift and supershift assays revealed specific binding of TCF-4 protein to the TCF sequence of the VCN promoter, and site-directed mutagenesis of the TCF site 492 bp diminished VCN-Luc activity. Our findings suggest that beta-catenin, through regulation of this versatile proteoglycan, VCN, augments the establishment of a provisional extracellular matrix (ECM) leading to normal or aberrant vascular injury and repair.