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dc.contributor.authorde Bruyn, Magali-
dc.contributor.authorBreynaert, Christine-
dc.contributor.authorARIJS, Ingrid-
dc.contributor.authorDe Hertogh, Gert-
dc.contributor.authorGeboes, Karel-
dc.contributor.authorThijs, Greet-
dc.contributor.authorMatteoli, Gianluca-
dc.contributor.authorHu, Jialiang-
dc.contributor.authorVan Damme, Jo-
dc.contributor.authorArnold, Bernd-
dc.contributor.authorFerrante, Marc-
dc.contributor.authorVermeire, Severine-
dc.contributor.authorVan Assche, Gert-
dc.contributor.authorOpdenakker, Ghislain-
dc.identifier.citationNATURE COMMUNICATIONS, 8, p. 1-15 (Art N° 15384)-
dc.description.abstractOne third of patients with inflammatory bowel disease (IBD) inadequately respond to anti-TNF treatment and preclinical data suggest that matrix metalloproteinase-9 (MMP-9) is a novel therapeutic target. Here we show that IBD clinical and histopathological parameters found in wild type mice challenged with three different models of colitis, acute and chronic dextran sodium sulphate (DSS), and acute 2,4,6-trinitrobenzenesulfonic acid-induced colitis are not attenuated in MMP-9 knockout mice. We find similar colonic gene expression profiles in wild type and MMP-9 knockout mice in control and acute DSS conditions with the exception of eleven genes involved in antimicrobial response during colitis. Parameters of chronic colitis are similar in wild type and MMP-9 knockout mice. Pharmacological inhibition of MMP-9 with bio-active peptides does not improve DSS colitis. We suggest that MMP-9 upregulation is a consequence rather than a cause of intestinal inflammation and we question whether MMP-9 represents a disease target in IBD.-
dc.description.sponsorshipM.d.B. and C.B. were supported by a PhD fellowship of the Agency for Innovation by Science and Technology in Flanders (IWT). G.O. and G.V.A. were supported by grants from the Research Foundation Flanders (FWO-Vlaanderen; grant number: G077513N and G069014). G.O. and J.V.D. were supported by the Concerted Research Actions of the Flemish Government (GOA 2013/015). I. A. is a Postdoctoral Researcher and S.V., G.V.A. and M.F. are Senior Clinical Investigators of FWO-Vlaanderen. G.M. received grant support from the KU Leuven (C12/15/016). This work was further supported by a grant from the Broad Medical Research Program of the Broad Foundation (IBD-0319R). We would like to thank Erik Martens (Laboratory of Immunobiology, Rega Institute for Medical Research) for assistance in experimental work with regard to gelatin zymography analyses at the Rega Institute for Medical Research, Jonathan Cremer (Laboratory of Clinical Immunology, KU Leuven) for assistance with histopathological analyses and Prof Dr Em. Jan Ceuppens for critical revision of the manuscript. In addition, our gratitude is also directed towards Dr Pedro J. Gomez Pinilla, Wiebe Vanhove and Brecht Creyns (Translational Research Center for Gastrointestinal Disorders/TARGID, KU Leuven and Laboratory of Clinical Immunology, KU Leuven) for their practical assistance with regard to the TNBS mouse model.-
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit (c) The Author(s) 2017-
dc.titleInhibition of gelatinase B/MMP-9 does not attenuate colitis in murine models of inflammatory bowel disease-
dc.typeJournal Contribution-
dc.description.notes[de Bruyn, Magali; Thijs, Greet; Opdenakker, Ghislain] Katholieke Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Lab Immunobiol, B-3000 Leuven, Belgium. [de Bruyn, Magali; Arijs, Ingrid; Matteoli, Gianluca; Ferrante, Marc; Vermeire, Severine; Van Assche, Gert] Katholieke Univ Leuven, Dept Clin & Expt Med, Translat Res Ctr Gastrointestinal Disorders TARGI, B-3000 Leuven, Belgium. [Breynaert, Christine] Katholieke Univ Leuven, Dept Microbiol & Immunol, Lab Clin Immunol, B-3000 Leuven, Belgium. [Arijs, Ingrid] Hasselt Univ, Fac Med & Life Sci, B-3500 Hasselt, Belgium. [De Hertogh, Gert; Geboes, Karel] Katholieke Univ Leuven, Dept Imaging & Pathol, Translat Cell & Tissue Res, B-3000 Leuven, Belgium. [Hu, Jialiang] China Pharmaceut Univ, Key Lab Modern Chinese Med, Minist Educ, Nanjing 211198, Jiangsu, Peoples R China. [Van Damme, Jo] Katholieke Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, Lab Mol Immunol, B-3000 Leuven, Belgium. [Arnold, Bernd] German Canc Res Ctr, Dept Mol Immunol, D-69120 Heidelberg, Germany. [Ferrante, Marc; Vermeire, Severine; Van Assche, Gert] Univ Hosp Leuven, Dept Gastroenterol & Hepatol, B-3000 Leuven, Belgium.-
item.fullcitationde Bruyn, Magali; Breynaert, Christine; ARIJS, Ingrid; De Hertogh, Gert; Geboes, Karel; Thijs, Greet; Matteoli, Gianluca; Hu, Jialiang; Van Damme, Jo; Arnold, Bernd; Ferrante, Marc; Vermeire, Severine; Van Assche, Gert & Opdenakker, Ghislain (2017) Inhibition of gelatinase B/MMP-9 does not attenuate colitis in murine models of inflammatory bowel disease. In: NATURE COMMUNICATIONS, 8, p. 1-15 (Art N° 15384).-
item.fulltextWith Fulltext-
item.accessRightsOpen Access-
item.validationecoom 2018-
item.contributorArnold, Bernd-
item.contributorOpdenakker, Ghislain-
item.contributorDe Hertogh, Gert-
item.contributorVermeire, Severine-
item.contributorBreynaert, Christine-
item.contributorGeboes, Karel-
item.contributorde Bruyn, Magali-
item.contributorARIJS, Ingrid-
item.contributorThijs, Greet-
item.contributorMatteoli, Gianluca-
item.contributorVan Assche, Gert-
item.contributorVan Damme, Jo-
item.contributorFerrante, Marc-
item.contributorHu, Jialiang-
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