title: The molecular biology of matrix metalloproteinases and tissue inhibitors of metalloproteinases in inflammatory bowel diseases.
abstract: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be predominant proteases and protease inhibitors involved in the pathogenesis of inflammatory bowel diseases (IBD) through their ability to remodel the extracellular matrix (ECM) in response to inflammatory stimuli and by their immunomodulating effects. An imbalance between MMPs and TIMPs has been linked with acute and chronic inflammation and aberrant tissue remodeling, as seen in IBD. Moreover, recurrent phases of tissue destruction and subsequent tissue repair can cause serious complications in IBD patients such as fistulas and fibrosis. The aims of this review are (i) to summarize current literature on genetic association, mRNA, and protein expression studies with regard to MMPs and TIMPs in IBD patients and various animal models, including those with transgenic and knockout mice; (ii) to compare biochemical and molecular biological data in humans with those obtained in animal model studies and (iii) to critically evaluate and translate how this knowledge may be used in practical terms to understand better the pathophysiology and mechanisms operating in IBD and to apply this for improvement of clinical outcomes at diagnostic, prognostic and therapeutic levels.
authors.affiliation: a Laboratory of Immunobiology, Department of Microbiology and Immunology, KU Leuven , Rega Institute for Medical Research , Leuven , Belgium.|b Department of Clinical and Experimental Medicine, KU Leuven , Translational Research Center for Gastrointestinal Disorders (TARGID) , Leuven , Belgium.
authors.forename: Magali
authors.initials: M
authors.lastname: de Bruyn
authors.affiliation: a Laboratory of Immunobiology, Department of Microbiology and Immunology, KU Leuven , Rega Institute for Medical Research , Leuven , Belgium.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Vandooren
authors.affiliation: a Laboratory of Immunobiology, Department of Microbiology and Immunology, KU Leuven , Rega Institute for Medical Research , Leuven , Belgium.
authors.forename: Estefania
authors.initials: E
authors.lastname: Ugarte-Berzal
authors.affiliation: b Department of Clinical and Experimental Medicine, KU Leuven , Translational Research Center for Gastrointestinal Disorders (TARGID) , Leuven , Belgium.|c Faculty of Medicine and Life Sciences , Hasselt University , Hasselt , Belgium.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Arijs
authors.affiliation: b Department of Clinical and Experimental Medicine, KU Leuven , Translational Research Center for Gastrointestinal Disorders (TARGID) , Leuven , Belgium.|d University Hospitals Leuven , Leuven , Belgium.
authors.forename: Séverine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: a Laboratory of Immunobiology, Department of Microbiology and Immunology, KU Leuven , Rega Institute for Medical Research , Leuven , Belgium.
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
mesh_terms: D000818:Animals; D005109:Extracellular Matrix / Q000187:drug effects / Q000276:immunology*; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D020782:Matrix Metalloproteinases / Q000276:immunology*; D060066:Protein Interaction Maps / Q000187:drug effects; D019714:Tissue Inhibitor of Metalloproteinases / Q000276:immunology*
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases
keywords: Adaptive immunity; IBD; MMP; TIMP; association studies; autoimmunity; degradome; inflammation; innate immune defense; interaction; network hypothesis; neutrophils; protease web; remnant epitopes