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Publication : Inhibition of gelatinase B/MMP-9 does not attenuate colitis in murine models of inflammatory bowel disease.

First Author  de Bruyn M Year  2017
Journal  Nat Commun Volume  8
Pages  15384 PubMed ID  28561062
Mgi Jnum  J:249540 Mgi Id  MGI:5921000
Doi  10.1038/ncomms15384 Citation  de Bruyn M, et al. (2017) Inhibition of gelatinase B/MMP-9 does not attenuate colitis in murine models of inflammatory bowel disease. Nat Commun 8:15384
abstractText  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.
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