Basic–alimentary tractTargeted Deletion of Metalloproteinase 9 Attenuates Experimental Colitis in Mice: Central Role of Epithelial-Derived MMP
Section snippets
Experimental Animals
The Animal Care Committee of the Emory University, Atlanta, Georgia, approved all procedures performed on animals. In addition, all experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals published by the US Public Health Service. MMP-9−/− mice and age- and sex-matched WT littermates were purchased from Jackson Laboratories (Bar Harbor, ME) and bred at our facility. Mice lacking MMP-9 show a normal phenotype except for developmental defects in long
MMP-9 Activity and Expression Are Induced During Experimental Colitis in Mice
We used the DSS-induced colitis model to investigate the level of gelatinolytic enzymes stimulated during the induction of colitis. DSS 3% was administered to WT and MMP-9−/− littermates for 6 days, after which the mice were killed, and colonic tissue was processed to estimate the gelatinolytic activity. To detect the gelatinolytic activity in protein extracts from water- or DSS-treated mice, we performed zymography by using gelatin as a substrate as described in the Materials and Methods
Discussion
To explore the direct evidence for the involvement and role of MMP-9 in the development of experimental colitis, mice with targeted disruption of the MMP-9 gene and WT mice were evaluated for the clinical and histopathologic manifestations of colitis induced by DSS and S typhimurium. Colitis induced by DSS is a well-established preclinical model for studying the pathophysiological aspects of intestinal inflammation, having features of human colitis.45, 53 The results presented here show that WT
References (69)
Clinical epidemiology of inflammatory bowel diseaseincidence, prevalence, and environmental influences
Gastroenterology
(2004)Inflammatory bowel diseaseetiology and pathogenesis
Gastroenterology
(1998)- et al.
Regulation of matrix biology by matrix metalloproteinases
Curr Opin Cell Biol
(2004) - et al.
Matrix metalloproteinase levels are elevated in inflammatory bowel disease
Gastroenterology
(1999) - et al.
The role of up-regulated serine proteases and matrix metalloproteinases in the pathogenesis of a murine model of colitis
Am J Pathol
(2000) - et al.
Expression and regulation of tissue inhibitor of metalloproteinase-1 and matrix metalloproteinases by intestinal myofibroblasts in inflammatory bowel disease
Am J Pathol
(2003) - et al.
Expression of matrix metalloproteinases-2 and -9 in intestinal tissue of patients with inflammatory bowel diseases
Dig Liver Dis
(2005) - et al.
MMP-9/gelatinase B is a key regulator of growth plate angiogenesis and apoptosis of hypertrophic chondrocytes
Cell
(1998) - et al.
Isolation of neutrophil precursors from bone marrow for biochemical and transcriptional analysis
J Immunol Methods
(1999) - et al.
A novel method in the induction of reliable experimental acute and chronic ulcerative colitis in mice
Gastroenterology
(1990)
Therapeutic manipulation of the enteric microflora in inflammatory bowel diseasesantibiotics, probiotics, and prebiotics
Gastroenterology
Altered expression of laminins in Crohn’s disease small intestinal mucosa
Am J Pathol
Mouse models for the study of Crohn’s disease
Trends Mol Med
Gelatinase Ba tuner and amplifier of immune functions
Trends Immunol
Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing, whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact
Blood
Matrix metalloproteinase gelatinase B (MMP-9) coordinates and effects epithelial regeneration
J Biol Chem
The serpin alpha1-proteinase inhibitor is a critical substrate for gelatinase B/MMP-9 in vivo
Cell
The immunology of mucosal models of inflammation
Annu Rev Immunol
The role of Th1/Th2 polarization in mucosal immunity
Nat Med
Differential expression of matrix metalloproteinases and their tissue inhibitors in colon mucosa of patients with inflammatory bowel disease
Gut
A major role for matrix metalloproteinases in T cell injury in the gut
J Immunol
Upregulation of matrix metalloproteinases in a model of T cell mediated tissue injury in the gutanalysis by gene array and in situ hybridisation
Gut
Divergent patterns of matrix metalloproteinase activity during wound healing in ileum and colon of rats
Gut
Patterns of matrix metalloproteinase and TIMP expression in chronic ulcers
Arch Dermatol Res
MMPs in the gutinflammation hits the matrix
Gut
Matrix metalloproteinasesa tail of a frog that became a prince
Nat Rev Mol Cell Biol
Matrix metalloproteinase-9-mediated dendritic cell recruitment into the airways is a critical step in a mouse model of asthma
J Immunol
The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis
J Immunol
Gelatinase B in multiple sclerosis and experimental autoimmune encephalomyelitis
Acta Neurol Belg
Gelatinase B-deficient mice are resistant to experimental bullous pemphigoid
J Exp Med
How matrix metalloproteinases regulate cell behavior
Annu Rev Cell Dev Biol
Matrix metalloproteinases as modulators of inflammation and innate immunity
Nat Rev Immunol
Expression of matrix metalloproteases in inflammatory bowel disease
Ann N Y Acad Sci
Tumour necrosis factor-alpha converting enzyme (TACE) activity in human colonic epithelial cells
Clin Exp Immunol
Cited by (224)
Phenotypic and Functional Diversity of Neutrophils in Gut Inflammation and Cancer
2024, American Journal of PathologyExploring the mechanism of Artemisia argyi chemical composition for ulcerative colitis based on network pharmacology
2023, Arabian Journal of ChemistryPathogenesis of Fistulating Crohn's Disease: A Review
2023, Cellular and Molecular Gastroenterology and HepatologyCitation Excerpt :Increased MMP activity is associated with immune-mediated tissue injury and is found in CD.39 Murine models of dextran sulfate sodium-colitis demonstrate the significance of MMPs, with selected deletion of MMP-9 conferring a protective effect.40-43 Tissue inhibitors of MMP (TIMPs) are the natural inhibitors of MMPs, secreted by MMP-producing cells.44
Diagnosis and Classification of Fistula from Inflammatory Bowel Disease and Inflammatory Bowel Disease-Related Surgery
2022, Gastrointestinal Endoscopy Clinics of North America
F.E.C., B.W., and M.V.-K. contributed equally to this article.
Supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK 02802, DK 064644, and DK 06411; an Elsevier Research Initiative Award; a Crohn’s and Colitis Foundation of America Senior Research Award (S.V.S); Grants DK 02831 (D.M), DK 61417 (A.T.G), and HL 68543 (J.R); and Digestive Disease Research Center Grant 5R24DK064399-02.