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Genes 2018, 9(2), 85;

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

Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, University of Southampton School of Medicine, Southampton SO17 1BJ, UK
University Hospital Southampton NHS FT, Tremona Road, Southampton SO16 6YD, UK
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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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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