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Published on: November 30, 2016
Differential miRNA-Gene Expression in M Cells in Response to Crohn's Disease-Associated AIEC
Anaïs Larabi1, Laurène Salesse1, Charlotte Cordonnier1
1M2iSH, UMR 1071 Inserm, Université Clermont Auvergne, INRAE USC 2018, CRNH, 63001 Clermont-Ferrand, France.
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.
Insights
Adherent-invasive Escherichia coli (AIEC) alters gene and microRNA (miRNA) expression in intestinal cells. This study reveals miRNA-mediated gene regulation during AIEC infection, enhancing understanding of Crohn's disease pathogenesis.
Area of Science:
- Microbiology
- Gastroenterology
- Molecular Biology
Background:
- Adherent-invasive Escherichia coli (AIEC) are implicated in Crohn's disease (CD) pathogenesis.
- AIEC colonize the ileal mucosa and can invade intestinal epithelial cells (IECs) and M cells.
- Gene and microRNA (miRNA) expression changes in response to AIEC infection in IECs and M cells are largely uncharacterized.
Purpose of the Study:
- To comprehensively analyze miRNA and gene expression profiles in human intestinal epithelial Caco-2 cells and an in vitro M-cell model.
- To investigate the impact of AIEC LF82 strain infection on these profiles under basal and infected conditions.
- To identify potential miRNA-mediated gene regulation mechanisms during AIEC infection.
Main Methods:
- Utilized human intestinal epithelial Caco-2 monolayers and an in vitro M-cell model.
- Performed comprehensive miRNA and gene profiling under basal and AIEC LF82 infected conditions.
- Conducted in silico analysis to predict miRNA-gene interactions.
Main Results:
- AIEC LF82 translocated through M cells but not Caco-2 monolayers.
- Identified differential gene expression and miRNA profiles between M cells and Caco-2 cells.
- Observed AIEC infection-induced changes in gene and miRNA profiles in both cell types.
- Discovered potential miRNA-mediated regulation of AIEC-dysregulated genes.
Conclusions:
- AIEC infection significantly alters gene and miRNA expression in intestinal epithelial and M cells.
- A miRNA-mediated regulatory mechanism is suggested in response to AIEC infection.
- This study provides insights into M cell biology and AIEC-host interactions relevant to Crohn's disease.
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