N-acetylglucosaminyltransferase V negatively regulates integrin α5β1-mediated monocyte adhesion and transmigration through vascular endothelium.

摘要: Changes in the expression of glycosyltransferases that branch N-linked glycans are associated with many physiological and pathological events, such as cell adhesion, migration, proliferation tumor malignancy. Here, altered levels N-acetylglucosaminyltransferase V (GnT-V) its product β(1,6)-linked GlcNAc monocytes were observed during inflammation. The effects GnT-V aberrant β(1,6) branching on monocyte adhesion through vascular endothelium transmigration investigated. During IFN-γ-induced inflammation, transendothelial migration THP-1 enhanced, significantly decreased. Expression shRNA vector cells reversed abnormal characteristics, indicating direct involvement N-glycosylation these biological effects. enhanced inhibited by functional blockade antibodies against integrin α5 or β1 knockdown cells, demonstrating α5β1 monocyte-endothelium interaction. However, IFN-γ treatment lowered β1, without affecting total protein subunits. Decreased caused marked enchancement integrin-induced phosphorylation focal kinase (FAK). augmented FAK-mediated ERK activation cells. Furthermore, inhibitor pre-treatment nearly abrogated highly elevated transmigration, concomitant reversal decrease branching. Our results demonstrate for first time decreased activity due to inflammatory cytokine induction human resulted α5β1-dependent monocyte-vascular transmigration. Consequently, elevation FAK phosphorylation. These promoted downstream signaling, including pathway, indicate may be a potential therapeutic target conditions.