Differential miRNA-Gene Expression in M Cells in Response to Crohn’s Disease-Associated AIEC

Abstract

Adherent-invasive Escherichia coli (AIEC), which abnormally colonize the ileal mucosa of Crohn’s disease (CD) patients, are able to invade intestinal epithelial cells (IECs) and translocate through M cells overlying Peyer’s patches. The levels of microRNA (miRNA) and gene expression in IECs and M cells upon AIEC infection have not been investigated. Here, we used human intestinal epithelial Caco-2 monolayers and an in vitro M-cell model of AIEC translocation to analyze comprehensive miRNA and gene profiling under basal condition and upon infection with the reference AIEC LF82 strain. Our results showed that AIEC LF82 translocated through M cells but not Caco-2 monolayers. Both differential gene expression and miRNA profile in M cells compared to Caco-2 cells were obtained. In addition, AIEC infection induces changes in gene and miRNA profiles in both Caco-2 and M cells. In silico analysis showed that certain genes dysregulated upon AIEC infection were potential targets of AIEC-dysregulated miRNAs, suggesting a miRNA-mediated regulation of gene expression during AIEC infection in Caco-2, as well as M cells. This study facilitates the discovery of M cell-specific and AIEC response-specific gene-miRNA signature and enhances the molecular understanding of M cell biology under basal condition and in response to infection with CD-associated AIEC.

A Systems Biology Approach to Identify Novel Biomarkers in Progression from Crohn’s Disease to Colorectal Cancer

“…A Systems Biology Approach to Identify Novel Biomarkers in Progression from Crohn's Disease to Colorectal Cancer factors (Larabi et al, 2020;Liu et al, 2015). Results of genome-wide association studies indicated that several genes have a role in inheritable vulnerability to CD.…”

The Role of the Lymphatic System in the Pathogenesis and Treatment of Inflammatory Bowel Disease

“…Various innate and adaptive immune cells are present in PPs including conventional B and T cells, plasma cells, CD4 + TCR-β + T-cells and γδ T-cells [74,75]. PPs have been shown to play an important role in the initiation of mucosal inflammation in patients with CD and in murine models, since bacteria, especially the adherent-invasive E.coli (AIEC) colonizing the PPs subepithelial dome, interact with resident DCs and, hence, acquire an inflammatory profile with elevated TLR-4 and TNF-a expression [76][77][78][79]. Th1 polarization has also been observed in the PPs of patients with active as compared to inactive CD, UC and healthy controls [80].…”

miRNAs Can Affect Intestinal Epithelial Barrier in Inflammatory Bowel Disease

“…Larabid et al. (2020) analyzed the dysregulated miRNAs and their potential target genes in AIEC infection of Caco-2-cl1 cells, and downregulated miR-31c-1-3p may target mucins ( MUC1) and claudin ( CLDN ) to disturb the intestinal barrier function of IBD patients ( 47 ). Moreover, a previous study had indicated that AIEC reduced expression of proteins required for autophagy through upregulating miR-30c and miR-130a in T84 cells and mouse enterocytes, thus conducting self-replication ( 6 ).…”