# 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)

## TL;DR

This study identifies GlcAT-S as a gene that protects the gut lining and reduces inflammation in a fruit fly model of intestinal damage.

## Contribution

The study discovers GlcAT-S as a novel gene involved in mucosal protection and intestinal inflammation in Drosophila.

## Key findings

- GlcAT-S knockdown in fruit flies reduces gut length and increases stem cell proliferation.
- GlcAT-S is linked to reduced mucus production and increased inflammatory gene expression.
- GlcAT-S may serve as a potential therapeutic target for inflammatory bowel disease.

## Abstract

The present study provides evidence that GlcAT-S plays a protective role in the maintenance of gut tissue integrity and the regulation of intestinal inflammation in a Drosophila gut-damage model. The disruption of the mucosal barrier is a key feature of inflammatory bowel disease, and understanding the mechanisms underlying this disruption and the subsequent inflammatory response is crucial for developing effective therapies. Using a combination of bioinformatics analysis and genetic manipulation, we identified GlcAT-S as a key gene that is involved in mucosal protection, as well as demonstrating its role in DSS-induced intestinal damage. Our findings suggest that GlcAT-S may serve as a potential therapeutic target for the treatment of inflammatory bowel disease.

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 Drosophila melanogaster 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 (GlcAT-S, Fibp, and Wisp in Drosophila), were selected as the relevant genes that respond 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 genes, 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 regulation of 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.