| First Author | Mao H | Year | 2026 |
| Journal | J Biol Chem | Volume | 302 |
| Issue | 2 | Pages | 111014 |
| PubMed ID | 41380967 | Mgi Jnum | J:378156 |
| Mgi Id | MGI:8279467 | Doi | 10.1016/j.jbc.2025.111014 |
| Citation | Mao H, et al. (2025) B3GNT8-mediated glycosylation maintains intestinal homeostasis and protects against colitis. J Biol Chem 302(2):111014 |
| abstractText | Emerging evidence suggests that alterations in intestinal epithelial glycosylation are implicated in the pathogenesis of inflammatory bowel disease (IBD). However, the intricate roles of gut glycosylation in maintaining intestinal homeostasis remain inadequately elucidated. Beta 1, 3-N-acetylglucosaminyltransferases (B3GNTs) are Golgi glycosyltransferases involved in the biosynthesis of poly-N-acetyl-lactosamine chains. In this study, we here create B3gnt8 knockout (B3gnt8(-/-)) mice to investigate its precise effects on intestinal homeostasis. Our findings reveal that both messenger RNA (mRNA) and protein levels of B3GNT8 are significantly diminished in the inflamed mucosa of pediatric IBD patients. Furthermore, the levels of B3GNT8 were negatively correlated with ulcerative colitis (UC) progression. B3gnt8(-/-) mice exhibited heightened vulnerability to Dextran sodium sulfate (DSS)-induced intestinal inflammation, characterized by compromised tight junction integrity and impaired secretion of Mucin from goblet cells. The loss of B3gnt8 resulted in a significant reduction in Paneth cell populations as well as diminished lysozyme content, leading to an altered composition and adhesion properties of intestinal bacteria. Additionally, B3gnt8 deficiency impaired lysosomal stability, potentially reducing glycosylation of lysosomal-associated membrane proteins half (LAMP1/2). From a mechanistic perspective, deficiency in B3gnt8 disrupted autophagy-lysosomal processes within Paneth cells may via the ATG16L1-ATG12-ATG5 pathway. Notably, the absence of B3gnt8 rendered these mice more susceptible to DSS-induced colitis. In conclusion, our findings identify B3GNT8 as a key player in intestinal epithelial glycosylation, thereby revealing a potential target for new IBD therapeutics. |
