Endomucin inhibits VEGF-induced endothelial cell migration, growth, and morphogenesis by modulating VEGFR2 signaling

• DOI: 10.1038/s41598-017-16852-x
• Publication Date: 2017-12-01T11:19:50Z
• Authors: Cindy Park-Windhol; Yin Shan Ng; Jinling Yang; Vincent Primo; Magali Saint-Geniez; Patricia A. D’Amore
• Keywords: Vascular Endothelial Growth Factor A; 0301 basic medicine; 570; Multidisciplinary; Neovascularization, Pathologic; Sialoglycoproteins; 610; Retinal Pigment Epithelium; Retinal Neovascularization; Vascular Endothelial Growth Factor Receptor-2; Article; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Cell Movement; Morphogenesis; Animals; Humans; Endothelium, Vascular; Phosphorylation; Cells, Cultured; Cell Proliferation; Signal Transduction

Angiogenesis is central to both normal and pathologic processes. Endothelial cells (ECs) express O-glycoproteins that are believed play important roles in vascular development stability. Endomucin-1 (EMCN) a type I O-glycosylated, sialic-rich glycoprotein, specifically expressed by venous capillary endothelium. Evidence has pointed potential role for EMCN angiogenesis but it had not been directly investigated. In this study, we examined the of modulating levels vivo vitro. Reduction led impairment during retinal vivo. To determine cellular basis inhibition, gain- loss-of-function studies were performed human EC (HREC) vitro over-expression using adenovirus or gene knockdown siRNA. We show reduced migration, inhibited cell growth without compromising survival, suppressed tube morphogenesis ECs, whereas increased proliferation formation. Furthermore, VEGF-induced signaling as measured decreased phospho-VEGFR2, phospho-ERK1/2 phospho-p38-MAPK levels. These results suggest novel potent regulator point its new therapeutic target angiogenesis-related diseases.