Glycocalyx regulation of vascular endothelial growth factor receptor 2 activity

ABSTRACT We have previously shown that knockdown of endomucin (EMCN), an integral membrane glycocalyx glycoprotein, prevents VEGF‐induced proliferation, migration, and tube formation in vitro and angiogenesis in vivo. In the endothelium, VEGF mediates most of its angiogenic effects through VEGF rece...

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Bibliographic Details
Published in:The FASEB journal 2019-08, Vol.33 (8), p.9362-9373
Main Authors: Leblanc, Michelle E., Saez‐Torres, Kahira L., Cano, Issahy, Hu, Zhengping, Saint‐Geniez, Magali, Ng, Yin‐Shan, D'Amore, Patricia A.
Format: Article
Language:English
Subjects:
angiogenesis
endocytosis
endothelium
VEGF
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Summary:ABSTRACT We have previously shown that knockdown of endomucin (EMCN), an integral membrane glycocalyx glycoprotein, prevents VEGF‐induced proliferation, migration, and tube formation in vitro and angiogenesis in vivo. In the endothelium, VEGF mediates most of its angiogenic effects through VEGF receptor 2 (VEGFR2). To understand the role of EMCN, we examined the effect of EMCN depletion on VEGFR2 endocytosis and activation. Results showed that although VEGF stimulation promoted VEGFR2 internalization in control endothelial cells (ECs), loss of EMCN prevented VEGFR2 endocytosis. Cell surface analysis revealed a decrease in VEGFR2 following VEGF stimulation in control but not siRNA directed against EMCN—transfected ECs. EMCN depletion resulted in heightened phosphorylation following VEGF stimulation with an increase in total VEGFR2 protein. These results indicate that EMCN modulates VEGFR2 endocytosis and activity and point to EMCN as a potential therapeutic target.—LeBlanc, M. E., Saez‐Torres, K. L., Cano, I., Hu, Z., Saint‐Geniez, M., Ng, Y.‐S., D'Amore, P. A. Glycocalyx regulation of vascular endothelial growth factor receptor 2 activity. FASEB J. 33, 9362–9373 (2019). www.fasebj.org
ISSN:0892-6638
1530-6860
DOI:10.1096/fj.201900011R