title: Divergent influence of microRNA-21 deletion on murine colitis phenotypes.
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+CD45RB High 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+CD45RB High T cells from miR-21 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.
authors.affiliation: Section of Gastroenterology, Department of Medicine, University of Chicago, Chicago, Illinois.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.forename: Fengshi
authors.initials: F
authors.lastname: Dong
authors.forename: Nikolai
authors.initials: N
authors.lastname: Arendovich
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Huang
authors.forename: John H
authors.initials: JH
authors.lastname: Kwon
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000502:physiology; D016264:Dextran Sulfate / Q000633:toxicity; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D015415:Biomarkers; D004268:DNA-Binding Proteins; C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D012333:RNA, Messenger; C499308:Rag2 protein, mouse; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate