B3GNT7 regulates mucin O-glycosylation to alleviate colonic inflammation

B3GNT7, an important glycosyltransferase highly expressed in intestinal epithelial cells, is involved in physiological processes in the intestine. This study presents novel findings on the potential role and mechanism of B3GNT7 in ulcerative colitis (UC). DSS-induced mouse model of colitis was established to investigate the expression of B3GNT7 in the colon using transcriptomics and immunohistochemistry. Bioinformatics analysis was conducted to explore the biological functions of B3GNT7. The correlation between the transcription levels of B3GNT7 in the colonic tissues of UC patients from the IBDMDB database was analyzed and the severity of colonic inflammation, along with potential mechanisms. The DSS-induced colitis mouse model was successfully established, and transcriptomic analysis revealed a significant downregulation of B3GNT7 expression in the colonic tissues compared to healthy mice. Functional enrichment analysis showed that the main biological function of B3GNT7 was to participate in the mucin O-glycosylation process. Protein interaction analysis indicates that the molecules showing strong interaction with B3GNT7 were members of the mucin MUC family, including MUC2, MUC3, and MUC6. In UC patients, the transcription levels of B3GNT7 were significantly decreased, particularly in patients with moderate to severe disease activity. The expression level of B3GNT7 was negatively correlated with the endoscopic severity of UC. Gene set enrichment analysis (GSEA) further revealed significant enrichment of B3GNT7 in the mucin O-glycosylation synthesis signaling pathway. The downregulation of B3GNT7 expression in the colonic tissues of UC may contribute to impaired mucin barrier function and the progression of colitis. Overall design: To establish an experimental colitis mice model, we induced colitis in mice by administering 2.5% DSS in their drinking water. On the 8th day, we compared the changes in body weight and colon length between the DSS Group and the control group (CON group). Colon tissue samples were collected for transcriptome sequencing (RNA-seq) analysis.