Divergent influence of MicroRNA-21 deletion on murine colitis phenotypes

Feng Wu, Fengshi Dong, Nikolai Arendovich, Jing Zhang, Yong Huang, John H. Kwon

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: MicroRNAs (miRNAs) acting as negative regulators of gene expression are differentially expressed in intestinal tissues of patients with inflammatory bowel disease (IBD). Assessing the functions of miRNAs in murine colitis facilitates elucidating the role of specific miRNAs in human IBD. We aimed to determine the miRNA signature of several models of colitis and to assess the influence of miR-21 on intestinal inflammation. Methods: miR-21-deficient mouse and littermate controls were assessed in the standard DSS, TNBS, and CD4+ T-cell transfer models of colitis. RNAs of mouse colon and CD4+CD45RBHigh cells were analyzed by miRNA and mRNA microarray, and quantitative reverse transcription polymerase chain reaction. T helper (Th) cell polarization was accessed by flow cytometry and enzyme-linked immunosorbent assay. Results: Alterations in miRNA expression were identified for acute and chronic DSS and TNBS colitis, respectively. The expression of miRs-21, -142-3p, and -223 were distinct between DSS and TNBS models while overlap of numerous miRNAs was found. Importantly, miRs-19b, -192, and -215, that are decreased in IBD, were decreased in these models of colitis. miR-21, which is increased in IBD, was increased in TNBS colitis. Furthermore, the deletion of miR-21 resulted in the exacerbation of both the TNBS and T-cell transfer models of colitis. CD4+CD45RBHigh T cells from miR-212/2 mice were prone to Th1 polarization. Conclusions: MiRNAs are differentially expressed in both human IBD and murine colitis, with overlap of several IBD-associated miRNAs. The demonstration that miR-21 deletion exacerbated CD4+ T-cell-mediated models of colitis provide further evidence that miRNAs play significant roles in the pathogenesis of IBD.

Original languageEnglish (US)
Pages (from-to)1972-1985
Number of pages14
JournalInflammatory Bowel Diseases
Volume20
Issue number11
DOIs
StatePublished - Jan 1 2014

    Fingerprint

Keywords

  • CD4+ T cells
  • Colitis model
  • Inflammatory bowel disease
  • MicroRNA
  • MiR-21

ASJC Scopus subject areas

  • Immunology and Allergy
  • Gastroenterology

Cite this

Wu, F., Dong, F., Arendovich, N., Zhang, J., Huang, Y., & Kwon, J. H. (2014). Divergent influence of MicroRNA-21 deletion on murine colitis phenotypes. Inflammatory Bowel Diseases, 20(11), 1972-1985. https://doi.org/10.1097/MIB.0000000000000201