Loss of VEGF-C or VEGFR3 function or gain of VE-cadherin function causes identical defects in sinusoidal and lymphatic growth, resulting in anemia and lymphedema. Mechanistically, VEGF-C drives VE-cadherin phosphorylation and endocytosis whereas VE-cadherin prevents VEGFR3 internalization and downstream growth factor signaling. In the absence of VEGFR3, reducing VE-cadherin levels rescues vascular growth by potentiating VEGF-C–VEGFR2 signaling.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Zou, Z. et al. The secreted lymphangiogenic factor CCBE1 is essential for fetal liver erythropoiesis. Blood 121, 3328–3236 (2013). This paper reports the role of CCBE1 in fetal liver hematopoiesis.
Fang, S. et al. Critical requirement of VEGF-C in transition to fetal erythropoiesis. Blood 128, 710–720 (2016). This paper reports the role of VEGF-C in fetal liver hematopoiesis.
Dartsch, N. et al. Fusing VE-cadherin to α-catenin impairs fetal liver hematopoiesis and lymph but not blood vessel formation. Mol. Cell Biol. 34, 1634–1648 (2014). This paper reports the effects of VE-cadherin gain-of-function on lymphatic and liver growth.
Esser, S. et al. Vascular endothelial growth factor induces VE-cadherin tyrosine phosphorylation in endothelial cells. J. Cell Sci. 111, 1853–1865 (1998). This paper demonstrates how VEGF induces VE-cadherin phosphorylation to control endothelial permeability.
Lampugnani, M. G. et al. Vascular endothelial cadherin controls VEGFR-2 internalization and signaling from intracellular compartments. J. Cell Biol. 174, 593–604 (2021). This paper shows how VE-cadherin inhibits VEGFR2 trafficking to endosomes, an event that is required for growth factor signaling.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Sung, D. C. et al. Sinusoidal and lymphatic vessel growth are controlled by reciprocal VEGF-C–CDH5 inhibition. Nat. Cardiovas. Res. https://doi.org/10.1038/s44161-022-00147-0 (2022).
Rights and permissions
About this article
Cite this article
VEGF signaling and cell adhesion interplay controls sinusoidal and lymphatic growth. Nat Cardiovasc Res 1, 986–987 (2022). https://doi.org/10.1038/s44161-022-00152-3
Published:
Issue Date:
DOI: https://doi.org/10.1038/s44161-022-00152-3
