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

The intestinal epithelium, which is 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 a mucus-disrupting agent, dextran sodium sulfate, to <i>Drosophila melanogaster</i> and screened 63 differentially expressed genes (DEGs). Through a 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 (<i>GlcAT-S</i>, <i>Fibp</i>, and <i>Wisp</i> in <i>Drosophila</i>), were selected as the relevant genes that respond to mucus disruption. We confirmed that enterocyte (EC)-specific <i>GlcAT-S</i> knockdown by RNAi significantly reduced gut length and increased intestinal stem cell proliferation in <i>Drosophila</i>. Additionally, in EC-specific <i>GlcAT-S</i>-knockdown flies, it was observed that the mucus-production-related genes, <i>Muc68D</i> and <i>Mur29B</i>, were specifically reduced, whereas the inflammatory cytokines <i>egr</i> and <i>upd3</i> were overexpressed. This study provides evidence that <i>GlcAT-S</i> is involved in the regulation of intestinal inflammation in <i>Drosophila</i> and plays a protective role against mucus disruption. Our findings suggest that <i>GlcAT-S</i> may be a potential therapeutic target for the treatment of intestinal inflammatory diseases such as IBD.