FUT8 promotes HDM-induced glycolysis, epithelial-mesenchymal transition and inflammation in bronchial epithelial cells by inducing N-glycosylation modification of GLUT1.

House dust mite (HDM) allergy impairs bronchial epithelial cells (BECs) function and promotes inflammation in asthma; mechanisms remain unclear. This study elucidates how fucosyltransferase 8 (FUT8) modulates HDM-induced epithelial-mesenchymal transition (EMT) and inflammatory responses in BECs via the core fucosylation of GLUT1-mediated glycolytic pathway. The BEC line BEAS-2B was treated with HDM to simulate an allergen exposure environment. Changes in cellular glycolysis were assessed using the following indicators: extracellular acidification rate (ECAR), ATP production, and lactate production. Changes in EMT were indicated by alterations in the expression levels of E-cadherin, vimentin, and N-cadherin. Inflammatory responses were monitored by the release of the pro-inflammatory molecules IL-25 and IL-33. The effect of FUT8 on GLUT1 glycosylation was investigated using the lectin pull-down assay. HDM treatment induced increased FUT8 expression. FUT8 silencing inhibited glycolysis, EMT, and the release of IL-25 and IL-33 in HDM-stimulated cells. Conversely, FUT8 overexpression promoted EMT and IL-25/IL-33 release; however, this effect was reversed by the glycolysis inhibitor 2-DG. FUT8 interacts with GLUT1 and promotes its N-glycosylation at the Asn45 site (N45), subsequently increasing its half-life. The attenuated glycolysis, EMT, and pro-inflammatory cytokine release (IL-25/IL-33) induced by FUT8 silencing were rescued by wild-type GLUT1 expression, but remained unaffected by expression of the GLUT1 (N45Q) mutant. This study elucidates a key mechanism whereby HDM, by inducing FUT8 expression, promotes core fucosylation of GLUT1. This modification enhances GLUT1-mediated glucose uptake and glycolytic flux, ultimately driving both EMT and robust inflammatory responses in BECs.