Wnt/beta-catenin signaling regulates Vascular Endothelial Growth Factor (VEGF) receptors in central nervous system endothelial cells
Year: 2026
Type: preprint
Abstract: In CNS endothelial cells (ECs), VEGF signaling promotes vascular permeability, and Wnt/beta-catenin signaling reduces vascular permeability by controlling the gene expression program for the blood-brain barrier. Here we show, using genetic mosaics, that, in mouse brain ECs in vivo , an increase in Wnt/beta-catenin signaling produces an increase in VEGFR1 levels and a decrease in VEGFR2 levels, and a decrease in Wnt/beta-catenin signaling produces a decrease in VEGFR1 levels and an increase in VEGFR2 levels. As VEGFR1 functions as a decoy receptor to reduce VEGF signaling through VEGFR2, these data imply that Wnt/beta-catenin signaling acts at the receptor level to reduce VEGF signaling. In HEK/293T cells, VEGF signaling is suppressed by Wnt/beta-catenin signaling in a dose-dependent manner, with nearly complete suppression observed at levels of Wnt/beta-catenin signaling that produce little or no change in VEGF receptor levels. These data reveal two mechanisms by which VEGF signaling is regulated by Wnt/beta-catenin signaling.
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7211935815