Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation

Journal of Cellular BiochemistryVolume 118, Issue 2 p. 298-307 Article Regulation of Laminin γ2 Expression by CDX2 in Colonic Epithelial Cells Is Impaired During Active Inflammation Mehmet Coskun, Corresponding Author Mehmet Coskun mehmet.coskun@regionh.dk 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 Correspondence to: Mehmet Coskun, Department of Gastroenterology, Medical Section 54 O3, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev DK-2730, Denmark. E-mail: mehmet.coskun@regionh.dkSearch for more papers by this authorChristoffer Soendergaard, Christoffer Soendergaard Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, DK-2730 DenmarkSearch for more papers by this authorSteffen Joergensen, Steffen Joergensen Department of Science, Systems and Models, Roskilde University, Roskilde, DK-4000 DenmarkSearch for more papers by this authorKatja Dahlgaard, Katja Dahlgaard Department of Science, Systems and Models, Roskilde University, Roskilde, DK-4000 DenmarkSearch for more papers by this authorLene Buhl Riis, Lene Buhl Riis Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, DK-2730 DenmarkSearch for more papers by this authorOle Haagen Nielsen, Ole Haagen Nielsen Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, DK-2730 DenmarkSearch for more papers by this authorAlbin Sandelin, Albin Sandelin The Bioinformatics Centre, Department of Biology and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, DK-2200 DenmarkSearch for more papers by this authorJesper Thorvald Troelsen, Jesper Thorvald Troelsen Department of Science, Systems and Models, Roskilde University, Roskilde, DK-4000 DenmarkSearch for more papers by this author Mehmet Coskun, Corresponding Author Mehmet Coskun mehmet.coskun@regionh.dk 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 Correspondence to: Mehmet Coskun, Department of Gastroenterology, Medical Section 54 O3, Herlev Hospital, University of Copenhagen, Herlev Ringvej 75, Herlev DK-2730, Denmark. E-mail: mehmet.coskun@regionh.dkSearch for more papers by this authorChristoffer Soendergaard, Christoffer Soendergaard Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, DK-2730 DenmarkSearch for more papers by this authorSteffen Joergensen, Steffen Joergensen Department of Science, Systems and Models, Roskilde University, Roskilde, DK-4000 DenmarkSearch for more papers by this authorKatja Dahlgaard, Katja Dahlgaard Department of Science, Systems and Models, Roskilde University, Roskilde, DK-4000 DenmarkSearch for more papers by this authorLene Buhl Riis, Lene Buhl Riis Department of Pathology, Herlev Hospital, University of Copenhagen, Herlev, DK-2730 DenmarkSearch for more papers by this authorOle Haagen Nielsen, Ole Haagen Nielsen Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, DK-2730 DenmarkSearch for more papers by this authorAlbin Sandelin, Albin Sandelin The Bioinformatics Centre, Department of Biology and Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, DK-2200 DenmarkSearch for more papers by this authorJesper Thorvald Troelsen, Jesper Thorvald Troelsen Department of Science, Systems and Models, Roskilde University, Roskilde, DK-4000 DenmarkSearch for more papers by this author First published: 23 June 2016 https://doi.org/10.1002/jcb.25636Citations: 6 Conflict of interest: None. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat 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. Citing Literature Volume118, Issue2February 2017Pages 298-307 RelatedInformation