VE‐cadherin N ‐glycosylation modified by N ‐acetylglucosaminyltransferase V regulates VE‐cadherin–β‐catenin interaction and monocyte adhesion

What is the central question of this study? Inflammation-induced monocyte adhesion is the initiator of most vascular diseases. The underlying mechanisms that mediate monocyte adhesion remain to be clarified fully. What is the main finding and its importance? N-acetylglucosaminyltransferase V (GnT-V)-mediated N-glycosylation of VE-cadherin regulates the dissociation of the VE-cadherin-β-catenin complex to modulate monocyte adhesion, but GnT-V overexpression cannot rescue monocyte adhesion induced by interleukin-1β. This study clarified the molecular mechanism of VE-cadherin in regulating the monocyte adhesion process.Monocyte adhesion is a crucial step in the initial stage of atherosclerosis, and dysfunction of VE-cadherin has been reported to be involved in this process. Our group previously found that VE-cadherin and its binding protein, β-catenin, were modified by sialylation, and the levels of sialylation were decreased in pro-inflammatory cytokine-treated human umbilical vein EA.hy926 cells. In this study, we confirmed that the sugar chains of VE-cadherin were modified by N-acetylglucosaminyltransferase V (GnT-V). We showed that the levels of GnT-V and β1,6-N-acetylglucosamine on the VE-cadherin were reduced in the presence of interleukin-1β, whereas the level of monocyte transendothelial migration was increased. Moreover, the interaction between VE-cadherin and β-catenin was increased, accompanied by an increased accumulation of degradative VE-cadherin and cytoplasmic β-catenin, indicating impairment of cell-cell junctions after interleukin-1β treatment. Furthermore, GnT-V short hairpin RNA and overexpression analysis confirmed that glycosylation of VE-cadherin was modified by GnT-V in EA.hy926 cells, which contributed to the monocyte-endothelial adhesion process. Taken together, these results suggest that the function of VE-cadherin in facilitating monocyte adhesion might result from the decreasing GnT-V expression and disorder of GnT-V-catalysed N-glycosylation. Our study clarified the molecular mechanism of VE-cadherin in regulation of the monocyte adhesion process and provided new insights into the post-transcriptional modifications of VE-cadherin.