title: Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation.
abstract: The expression of Caudal-related homeobox transcription factor 2 (CDX2) is impaired by tumor necrosis factor-α (TNF-α)-mediated activation of nuclear factor-κB (NF-κB) in ulcerative colitis (UC). Laminin subunit γ2 (LAMC2) is an epithelial basement membrane protein implicated in cell migration, proliferation, differentiation, as well as tumor invasion and intestinal inflammation, and its expression is enhanced by TNF-α in a NF-κB-dependent regulation of the recently identified LAMC2 enhancer. The aim was to determine whether CDX2 is involved in the basal regulation of LAMC2 in epithelial cells and to assess the influence of inflammation. Transcriptional regulation of LAMC2 was examined by reporter gene assays, overexpression, and shRNA-mediated knock-down of CDX2. CDX2-DNA interactions were assessed by chromatin immunoprecipitation on Caco-2 cells without or with TNF-α, as well as in purified colonic human epithelial cells. Immunohistochemical staining and quantitative reverse-transcription polymerase chain reaction analyses were used to measure the expression of CDX2 and LAMC2 in colonic biopsies from healthy controls and patients with UC. These data indicate that CDX2 directly regulates LAMC2 gene expression through interaction with elements in the LAMC2 promoter region. We further revealed an inverse effect of inflammation on CDX2 and LAMC2. The data presented provide a novel insight into how CDX2 is implicated in the transcriptional regulation of LAMC2 in intestinal epithelial cells, a function that is impaired during mucosal inflammation where a high level of TNF-α is present. J. Cell. Biochem. 118: 298-307, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, DK-2730, Denmark.|The Bioinformatics Centre, Department of Biology and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, DK-2200, Denmark.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Coskun
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, DK-2730, Denmark.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Soendergaard
authors.affiliation: Department of Science, Systems and Models, Roskilde University, Roskilde, DK-4000, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Joergensen
authors.affiliation: Department of Science, Systems and Models, Roskilde University, Roskilde, DK-4000, Denmark.
authors.forename: Katja
authors.initials: K
authors.lastname: Dahlgaard
authors.affiliation: Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, DK-2730, Denmark.
authors.forename: Lene Buhl
authors.initials: LB
authors.lastname: Riis
authors.affiliation: Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, DK-2730, Denmark.
authors.forename: Ole Haagen
authors.initials: OH
authors.lastname: Nielsen
authors.affiliation: The Bioinformatics Centre, Department of Biology and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, DK-2200, Denmark.
authors.forename: Albin
authors.initials: A
authors.lastname: Sandelin
authors.affiliation: Department of Science, Systems and Models, Roskilde University, Roskilde, DK-4000, Denmark.
authors.forename: Jesper Thorvald
authors.initials: JT
authors.lastname: Troelsen
mesh_terms: D000071616:CDX2 Transcription Factor / Q000096:biosynthesis*; D018938:Caco-2 Cells; D003092:Colitis / Q000378:metabolism* / Q000473:pathology; D003106:Colon; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007797:Laminin / Q000378:metabolism*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C400567:LAMC2 protein, human; D007797:Laminin; D014409:Tumor Necrosis Factor-alpha
keywords: CDX2; GENE REGULATION; INFLAMMATION; LAMC2; ULCERATIVE COLITIS