MicroRNAs and the hypoxic environment as modulators of the intestinal glycome during Inflammatory Bowel Diseases

GARCÍA, PABLO ALFREDO ; BANNOUD, NADIA; CUTINE, ANABELA; CAGNONI, ALEJANDRO J; CROCI, DIEGO O.; MARIÑO, KARINA VALERIA

Los Cocos, Cordoba

Simposio; Advanced Course on Mucosal Immunology (ACMI 2018), Society of Mucosal Immunology; 2018

Society of Mucosal Immunology

The intestinal epithelium is placed between the anaerobic lumen and a highly metabolic lamina propria. Supported by a complex vasculature, this barrier is affected by decreased blood flow and consequent tissue hypoxia, particularly during the inflammatory process in Inflammatory Bowel Disease (IBD) patients.In spite of the fact that the cell glycome can mediate several biological processes such as cell adhesion, host-pathogen interactions and immune modulation, studies on key factors regulating glycosylation during IBD are still scarce. In this is work, we aim to evaluate microRNAs as glycome modulatorsin human intestinal epithelial cells during hypoxia. We started by comparing a series of curated databases to cross match published micro-interferent RNAs (miRNAs) that were dysregulated both by hypoxia and IBD, and predictive databases of putative miRNAs targets. Our results indicate dysregulationduring IBD, of several miRNAs including hsa-miR-125a-5p and 140-5p that have high sequence complementarity with alpha-(2,6)-sialyltransferases (e.g. ST6GalNAc1), fucosyltransferases (such as FUT4), GlcNAc transferases (MGAT1, MGAT4) and alpha-mannosidases (MAN1A). Using HCT 116 cells as amodel cell line for colon epithelial cells, we evaluated glycome alterations in hypoxic conditions by flow cytometry both in 2D and 3D cultures (spheroids). Interestingly, we found altered exposure of high mannose N-glycans, as well as aberrant Galbeta 1,4GlcNAcbeta1,6(GlcNAcbeta 1,2Man alpha 1,3)Man-alpha1,3-, and downregulated terminal LAcNac groups (P