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Crohn's Disease–Associated Adherent Invasive Escherichia coli Modulate Levels of microRNAs in Intestinal Epithelial Cells to Reduce Autophagy
Abstract
Background & aims Levels of microRNAs are altered in intestinal tissues of patients with Crohn's disease (CD). The adherent-invasive Escherichia coli (AIEC), which colonize the ileal mucosa of patients with CD, adhere to and invade intestinal epithelial cells. We investigated the mechanism by which AIEC infection alters the expression of microRNAs and the host immune response. Methods Levels of microRNAs in human intestinal epithelial T84 cells and in mouse enterocytes were measured using quantitative reverse-transcription polymerase chain reaction. Luciferase assays were used to measure binding of microRNAs to the 3'-untranslated region of messenger RNA targets. Binding of nuclear factor-κB to promoters of genes encoding microRNAs was assessed by chromatin immunoprecipitation assays. Autophagy was measured by immunoblot analyses and immunofluorescent labeling of LC3. Anti-microRNAs were transferred to mice using ileal loops. Biopsy specimens from the terminal ileum of patients with ulcerative colitis (n = 20), CD (n = 20), or individuals without inflammatory bowel disease undergoing surveillance colonoscopies (controls, n = 13) were collected during endoscopic examination. Results AIEC infection up-regulated levels of microRNA (MIR) 30C and MIR130A in T84 cells and in mouse enterocytes by activating nuclear factor-κB. Up-regulation of these microRNAs reduced the levels of ATG5 and ATG16L1 and inhibited autophagy, leading to increased numbers of intracellular AIEC and an incr…
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“Although less work has been done on post-transcriptional regulation, several studies implicate microRNAs in controlling the expression of proteins associated with autophagy [334-336, 984-987].”
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Metadata
- Authors
- Nguyen, H. T. T., Dalmasso, G., Müller, S., Carrière, J., Seibold, F., & Darfeuille–Michaud, A.
- Venue
- Gastroenterology
- Publisher
- Elsevier BV
- Published
- 2014-02
- Volume
- 146
- Issue
- 2
- Pages
- 508-519
- ISSN
- 0016-5085
- Cited by
- 245
- References
- 3
- Language
- en
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