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Title: Inhibition of gelatinase B/MMP-9 does not attenuate colitis in murine models of inflammatory bowel disease
Authors: de 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
Issue Date: 2017
Source: NATURE COMMUNICATIONS, 8, p. 1-15 (Art N° 15384)
Abstract: One 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.
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.
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ISSN: 2041-1723
e-ISSN: 2041-1723
DOI: 10.1038/ncomms15384
ISI #: 000402388900001
Rights: This 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
Category: A1
Type: Journal Contribution
Validations: ecoom 2018
Appears in Collections:Research publications

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