Wnt/beta-catenin signaling regulates Vascular Endothelial Growth Factor (VEGF) receptors in central nervous system endothelial cells
- 1Howard Hughes Medical Institute, Johns Hopkins University School of Medicine
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.
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BibTeX
@misc{nathans2026wntbetacatenin,
title = {{Wnt/beta-catenin signaling regulates Vascular Endothelial Growth Factor (VEGF) receptors in central nervous system endothelial cells}},
author = {J. Nathans and Y. Wang and N. Zhu and A. Rattner and P. M. Smallwood},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.03.745507},
url = {https://www.biorxiv.org/content/10.64898/2026.09.03.745507v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Wnt/beta-catenin signaling regulates Vascular Endothelial Growth Factor (VEGF) receptors in central nervous system endothelial cells
AU - J. Nathans
AU - Y. Wang
AU - N. Zhu
AU - A. Rattner
AU - P. M. Smallwood
PY - 2026
DA - 2026/09/03
PB - bioRxiv
DO - 10.64898/2026.09.03.745507
UR - https://www.biorxiv.org/content/10.64898/2026.09.03.745507v1
AB - 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.
ER -