MiRNA expression profiling of intestinal epithelial cells from a spontaneous mice model of ulcerative colitis

ABSTRACT: Increased intestinal permeability is associated to the onset of inflammatory bowel disease (IBD) since the exposition to luminal content causes an immunological response that promotes intestinal inflammation. Several studies have been shown that microRNAs (miRNAs) are involved in IBD pathogenesis. Here, we aimed to functionally characterize the role of miRNAs in the regulation of intestinal permeability. miRNA profile of intestinal epithelial cells (IECs) isolated by colon of a UC mice model were identified using microarray. To predict the target genes of modulated miRNAs, we performed a bioinformatic analysis. To validate biologically miRNA targets, we performed transient transfection experiments in HT-29, Caco2 and T84 cell lines. To assess their role in barrier function, trans-epithelial electrical resistance and dextran flux assays were used. To investigate the in vivo effect of miR-195-5p, we employed a DSS-induced colitis model in mice. We identified 18 deregulated miRNAs in IECs from UC mice model and control mice. Among them, down-regulated miR-195-5p targeted CLDN2 and are involved in altered intestinal permeability. CLDN2 expression levels were increased in UC mice models and negatively correlated with the miR-195-5p expression. We demonstrated that the gain-of-function of miR-195-5p in colonic epithelial cell lines decreased the CLDN2 levels. We in vitro confirmed that miR-195-5p was able to control the intestinal barrier integrity. We also in vivo demonstrated that miR-195-5p attenuated the colonic inflammatory response in DSS-induced colitis and reduced the colonic permeability. All together our data support a previously unreported role of miR-195-5p in intestinal permeability and provide a potential pharmacological target for new therapeutic approaches in IBD.

ORGANISM(S): Mus musculus

PROVIDER: GSE183896 | GEO | 2022/04/27

REPOSITORIES: GEO