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dc.contributor.authorBrenna, Øystein
dc.contributor.authorBruland, Torunn
dc.contributor.authorFurnes, Marianne Waldum
dc.contributor.authorGranlund, Atle Van Beelen
dc.contributor.authorDrozdov, Ignat
dc.contributor.authorEmgård, Johanna
dc.contributor.authorBrønstad, Gunnar
dc.contributor.authorKidd, Mark
dc.contributor.authorSandvik, Arne Kristian
dc.contributor.authorGustafsson, Björn
dc.identifier.citationScandinavian Journal of Gastroenterology. 2015, 50 (10), 1241-1252.nb_NO
dc.description.abstractObjective. Activation of membrane receptor guanylate cyclase-C (GC-C) is implicated in gastrointestinal fluid and electrolyte balance, preservation of intestinal barrier integrity, anti-trophic effects and inhibition of pain sensation. To evaluate GC-C signaling, we examined the regulation of GC-C (GUCY2C/Gucy2c) and its endogenous ligands guanylin (GN/GUCA2A/Guca2a) and uroguanylin (UGN/GUCA2B/Guca2b) in colonic Crohn’s disease (CD), ulcerative colitis (UC) and in rats with 2,4,6-Trinitrobenzene sulphonic acid (TNBS) colitis. Correlation analyses between expression of GUCA2A and GUCY2C and expression of inflammatory cytokines (IL1A, IL1B, TNFA and IFNG) were conducted. Additionally, expression of transcription factors for GUCA2A and GUCY2C, and the GC-C signaling pathway, were examined. Material and methods. Biopsies from active UC/CD, un-inflamed UC/CD and healthy controls, and inflamed and healthy rat colon were investigated with gene expression microarray, immunohistochemistry (IHC) and in situ hybridization (ISH). Results. GUCA2A/Guca2a, GUCA2B, GUCY2C/Gucy2c, transcription factors, as well as several cyclic guanosine-3′,5′-monophosphate downstream mediators were all significantly down-regulated in both inflamed colonic inflammatory bowel disease (IBD) mucosa and TNBS colitis. Expression of GUCA2A and GUCY2C negatively correlated to expression of inflammatory cytokines. IHC and ISH confirmed microarray results for GUCA2A/Guca2a and GUCY2C/Gucy2c in inflamed samples. We identified a highly significant positive correlation between the expression of the transcription factor caudal type homeobox 2 (CDX2) and the expression of the downstream target gene GUCY2C. Conclusions. GUCA2A, GUCA2B and GUCY2C as well as several steps of the GC-C signaling pathway are down-regulated in IBD. This may have implications in IBD pathogenesis.nb_NO
dc.publisherTaylor & Francisnb_NO
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.titleThe guanylate cyclase-C signaling pathway is down-regulated in inflammatory bowel diseasenb_NO
dc.typeJournal articlenb_NO
dc.typePeer reviewednb_NO
dc.source.journalScandinavian Journal of Gastroenterologynb_NO
dc.relation.projectNorges forskningsråd: 223255nb_NO
dc.description.localcode2015 The Author(s). Published by Taylor & Francis. This is an Open Access article distributed under the terms of the Creative Commons AttributionNonCommercial-NoDerivatives License (, which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.nb_NO
cristin.unitnameInstitutt for klinisk og molekylær medisin

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Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal
Med mindre annet er angitt, så er denne innførselen lisensiert som Attribution-NonCommercial-NoDerivatives 4.0 Internasjonal