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miR-19b downregulates intestinal SOCS3 to reduce intestinal inflammation in Crohn's disease
Journal article   Open access   Peer reviewed

miR-19b downregulates intestinal SOCS3 to reduce intestinal inflammation in Crohn's disease

Xiuqin Cheng, Xiaofei Zhang, Jiewen Su, Yingdi Zhang, Weimei Zhou, Jun Zhou, Cheng Wang, Hongwei Liang, Xi Chen, Ruihua Shi, …
Scientific reports, v 5(1), pp 10397-10397
22 May 2015
DOI: https://doi.org/10.1038/srep10397
PMID: 25997679
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://www.nature.com/articles/srep10397.pdfView
Published, Version of Record (VoR) Open
url
https://doi.org/10.1038/srep10397View
Published, Version of Record (VoR) Open

Abstract

3' Untranslated Regions Adult Animals Base Sequence Caco-2 Cells Chemokine CCL20 - metabolism Chemokines - metabolism Colitis - chemically induced Colitis - pathology Colitis - prevention & control Crohn Disease - genetics Crohn Disease - pathology Down-Regulation - drug effects Female HT29 Cells Humans Immunohistochemistry In Situ Hybridization, Fluorescence Intestinal Mucosa - metabolism Male Mice MicroRNAs - antagonists & inhibitors MicroRNAs - genetics MicroRNAs - metabolism Middle Aged Rats Real-Time Polymerase Chain Reaction RNA Interference RNA, Messenger - metabolism RNA, Small Interfering - metabolism RNA, Untranslated - metabolism Sequence Alignment Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins - antagonists & inhibitors Suppressor of Cytokine Signaling Proteins - genetics Suppressor of Cytokine Signaling Proteins - metabolism Trinitrobenzenesulfonic Acid - toxicity
Although aberrant microRNA (miRNA) expression has frequently been observed in inflammatory bowel disease (IBD), its biological functions and targets remain largely unknown. Present study found that miR-19b was significantly downregulated in active Crohn's disease (CD). Using bioinformatics analysis, suppressor of cytokine signalling 3 (SOCS3), a physiological regulator of innate and adaptive immunity that controls several immuno-inflammatory diseases, was predicted to be a potential target of miR-19b. An inverse correlation between miR-19b and SOCS3 protein levels, but not mRNA, was identified in active-CD intestinal tissue samples. By overexpressing or knocking down miR-19b in Caco2 cells and HT29 cells, it was experimentally validated that miR-19b is a direct regulator of SOCS3. Using a luciferase reporter assay, it was confirmed that miR-19b directly recognizes the 3'-untranslated region (3'-UTR) of SOCS3. Furthermore, overexpression of miR-19b decreased SOCS3 expression, leading to increased production of macrophage-inflammatory protein-3α (MIP-3α) in Caco2 cells. In contrast, knockdown of miR-19b increased SOCS3 and decreased MIP-3α. Finally, intracolonically delivered miR-19b decreased the severity of colitis induced with 2,4,6-trinitrobenzene sulphonic acid (TNBS). Taken together, our findings suggest that miR-19b suppresses the inflammatory response by inhibiting SOCS3 to modulate chemokine production in intestinal epithelial cells (IECs) and thereby prevents the pathogenesis of CD.

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Collaboration types
Domestic collaboration
Web of Science research areas
Immunology
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