title: Profiles of microRNA networks in intestinal epithelial cells in a mouse model of colitis.
abstract: Inflammatory bowel diseases (IBDs) accompany a critical loss of the frontline barrier function that is achieved primarily by intestinal epithelial cells (IECs). Although the gene-regulation pathways underlying these host-defense roles of IECs presumably are deranged during IBD pathogenesis, the quantitative and qualitative alterations of posttranscriptional regulators such as microRNAs (miRNAs) within the cells largely remain to be defined. We aimed to uncover the regulatory miRNA-target gene relationships that arise differentially in inflamed small- compared with large-IECs. Whereas IBD significantly increased the expression of only a few miRNA candidates in small-IECs, numerous miRNAs were upregulated in inflamed large-IECs. These marked alterations might explain why the large, as compared with small, intestine is more sensitive to colitis and shows more severe pathology in this experimental model of IBD. Our in-depth assessment of the miRNA-mRNA expression profiles and the resulting networks prompts us to suggest that miRNAs such as miR-1224, miR-3473a, and miR-5128 represent biomarkers that appear in large-IECs upon IBD development and co-operatively repress the expression of key anti-inflammatory factors. The current study provides insight into gene-regulatory networks in IECs through which dynamic rearrangement of the involved miRNAs modulates the gene expression-regulation machinery between maintaining and disrupting gastrointestinal homeostasis.
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.|Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan.
authors.forename: Juneyoung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.|Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Mie 514-8507, Japan.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Yuki
authors.affiliation: Laboratory of Bioinformatics, National Institute of Biomedical Innovation, Osaka 567-0085, Japan.
authors.forename: Shandar
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Laboratory of Bioinformatics, National Institute of Biomedical Innovation, Osaka 567-0085, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Mizuguchi
authors.affiliation: Laboratory of Adjuvant Innovation, National Institute of Biomedical Innovation, Osaka 567-0085, Japan.|Laboratory of Vaccine Science, Immunology Frontier Research Center, World Premier Institute, Osaka University, Osaka 565-0871, Japan.
authors.forename: Ken J
authors.initials: KJ
authors.lastname: Ishii
authors.affiliation: Department of Molecular Pathobiology and Cell Adhesion Biology, Mie University Graduate School of Medicine, Mie 514-8507, Japan.
authors.forename: Motomu
authors.initials: M
authors.lastname: Shimaoka
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.|International Research and Development Center for Mucosal Vaccine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.|Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Chiba 277-8561, Japan.|Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency, Tokyo 102-0075, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D003092:Colitis / Q000235:genetics*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D015212:Inflammatory Bowel Diseases / Q000235:genetics / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D009928:Organ Specificity / Q000235:genetics; D059467:Transcriptome
chemical_list: D035683:MicroRNAs