Galnt3, an enzyme engaged in protein glycosylation modification, is essential for the maintaining of intestinal health in zebrafish.

Intestinal inflammation significantly impairs intestinal function and is closely associated with various health complications. Understanding its molecular mechanisms is crucial for developing effective therapeutic strategies. Galnt3, a member of the polypeptide N-acetylgalactosaminyltransferase family, participates in multiple biological processes, yet its specific role in intestinal inflammation remains poorly understood. In this study, we observed a significant downregulation of zebrafish galnt3 in response to GCRV virus or poly(I:C) infection. Galnt3 knockout (galnt3) zebrafish exhibited reduced survival rates, particularly following GCRV virus inoculation, accompanied by severe ascites and abdominal hemorrhage. Histopathological examination of intestinal tissues revealed thinning of intestinal walls, shortened villi, and increased acidic mucus secretion, all indicative of aggravated intestinal inflammation. Furthermore, galnt3 deficiency was found to trigger the upregulation of numerous pro-inflammatory cytokine genes. Through cell scratch assays and p38 MAPK phosphorylation analysis, we demonstrated that Galnt3 inhibits p38 MAPK phosphorylation and macrophage migration, thereby reducing the production of pro-inflammatory factors. Our findings highlight the pivotal role of Galnt3 in maintaining intestinal homeostasis and regulating inflammatory responses, providing valuable insights into the molecular mechanisms underlying intestinal inflammation and identifying potential therapeutic targets.