Identification of a Glucuronyltransferase-Related Gene, GlcAT-S with Putative Mucus Protection and Anti-Inflammatory Effects from Gut-Damaged Drosophila by DSS

The intestinal epithelium, protected by mucosal surfaces composed of mucins and other glycoproteins, functions as a selective barrier that absorbs nutrients while preventing the translocation of harmful substances. To understand the mechanisms between mucosal disruption and tissue inflammation, we orally administrated mucus-disrupting agent, dextran sodium sulfate to Drosophila melanogaster and screened 63 differentially expressed genes (DEGs). Through database search using bioinformatics tools (CHEA3 and WebGestalt), we identified ELK1 as a potential key transcription factor for the selected DEGs, and among the 63 DEGs, ELK1-related genes, B3GAT3, FIBP, and TENT2 (GlcAT-S, Fibp, and Wisp in Drosophila), were selected as relevant genes responding to mucus disruption. We confirmed that enterocyte (EC)-specific GlcAT-S knockdown by RNAi significantly reduced gut length and increased intestinal stem cell proliferation in Drosophila. Additionally, in EC-specific GlcAT-S knockdown flies, it was observed that the mucus production-related gene, Muc68D and Mur29B, were specifically reduced, whereas the inflammatory cytokines egr and upd3, were overexpressed. This study provides evidence that GlcAT-S is involved in the regulatiing intestinal inflammation in Drosophila and plays a protective role against mucus disruption. Our findings suggest that GlcAT-S may be a potential therapeutic target for the treatment of intestinal inflammatory diseases such as IBD.