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Glycocalyx regulation of vascular endothelial growth factor receptor 2 activity
Author(s) -
Leblanc Michelle E.,
SaezTorres Kahira L.,
Cano Issahy,
Hu Zhengping,
SaintGeniez Magali,
Ng YinShan,
D'Amore Patricia A.
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900011r
Subject(s) - glycocalyx , internalization , microbiology and biotechnology , endocytosis , angiogenesis , kinase insert domain receptor , vascular endothelial growth factor , chemistry , endothelial stem cell , stimulation , receptor , vascular endothelial growth factor a , biology , cancer research , endocrinology , in vitro , vegf receptors , biochemistry
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