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Genes 2018, 9(2), 85; https://doi.org/10.3390/genes9020085

MicroRNA-31 and MicroRNA-155 Are Overexpressed in Ulcerative Colitis and Regulate IL-13 Signaling by Targeting Interleukin 13 Receptor α-1

1
Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, University of Southampton School of Medicine, Southampton SO17 1BJ, UK
2
University Hospital Southampton NHS FT, Tremona Road, Southampton SO16 6YD, UK
3
School of Immunology and Microbial Sciences. MRC-Asthma UK Centre in Allergic Mechanisms of Asthma, Guy’s Campus King’s College, London SE1 9RT, UK
These authors contributed equally to this work.
Joint senior authors.
*
Author to whom correspondence should be addressed.
Received: 13 December 2017 / Revised: 1 February 2018 / Accepted: 5 February 2018 / Published: 13 February 2018
(This article belongs to the Section Human Genomics and Genetic Diseases)
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Abstract

Interleukin-13 (IL-13) is an important Type 2 T helper (Th2) cytokine, controlling biological functions in epithelium and has been linked to asthma, atopic dermatitis and ulcerative colitis (UC). Interleukin-13 signals through IL-13 receptor α-1 (IL13RA1 (gene) and IL13Rα1 (protein)), a receptor that can be regulated by microRNAs (miRs). MicroRNAs are small non-coding single-stranded RNAs with a role in several pathologies. However, their relevance in the pathophysiology of UC, a chronic inflammatory condition of the colonic mucosa, is poorly characterised. Here, we determined the expression of IL13Rα1 in UC, its potential regulation by miRs and the subsequent effect on IL-13 signalling. Inflamed mucosa of UC patients showed decreased mRNA and protein expression of IL13RA1 when compared to healthy controls. We show that miR-31 and miR-155 are upregulated in inflamed UC mucosa and that both directly target the 3′ untranslated region of IL13RA1 mRNA. Transfection of miR-31 and miR-155 mimics reduced the expression of IL13RA1 mRNA and protein, and blocked IL-13-dependent phosphorylation of signal transducer and activator of transcription 6 (STAT6) in HT-29 cells, a gut epithelium cell line. Interleukin-13 activation of suppressor of cytokine signaling 1 (SOCS1) and eotaxin-3 (CCL26) expression was also diminished. MicroRNA-31/microRNA-155 mimics also downregulated IL13RA1 in ex vivo human inflamed UC biopsies. We propose that miR-31 and miR-155 have an important role in limiting IL-13 signalling in UC disease. View Full-Text
Keywords: ulcerative colitis; microRNAs; interleukin-13; inflammation; epithelium; gut ulcerative colitis; microRNAs; interleukin-13; inflammation; epithelium; gut
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Gwiggner, M.; Martinez-Nunez, R.T.; Whiteoak, S.R.; Bondanese, V.P.; Claridge, A.; Collins, J.E.; Cummings, J.R.F.; Sanchez-Elsner, T. MicroRNA-31 and MicroRNA-155 Are Overexpressed in Ulcerative Colitis and Regulate IL-13 Signaling by Targeting Interleukin 13 Receptor α-1. Genes 2018, 9, 85.

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