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Matrix Metalloproteinases

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Crohn's Disease and Ulcerative Colitis

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Abstract

Matrix metalloproteinases (MMPs) belong to the protease superfamily of metzincins, which also includes snake venom MMPs and the adamalysins, also known as A Disintegrin and A Metalloproteinase-containing proteases (ADAMs) [1]. MMPs are structurally related, as they contain a catalytic domain with a highly conserved zinc-binding sequence essential for their action, and a pro-domain, which maintains the enzyme in inactive form and is cleaved by trypsin, plasmin, plasminogen or active MMPs during the activation process [2]. MMPs can collectively degrade all extracellular matrix (ECM) components [3] and, according to their main substrates, have been traditionally classified as collagenases, such as MMP-1 (collagenase 1), MMP-8 (collagenase 2) and MMP-13 (collagenase 3); gelatinases, including MMP-2 (gelatinase A) and MMP-9 (gelatinase B); stromelysins, such as MMP-3 (stromelysin 1), MMP-10 (stromelysin 2) and MMP-11; matrilysins, including MMP-7 and MMP-26; macrophage metalloelastase (MMP-12) [4]. The majority of MMPs are released into the ECM, whereas membrane-bound (MT)-MMPs are activated intracellularly by furin and subsequently anchored to the cell surface by a transmembrane domain [5]. MMPs can be produced by most immune and non immune cells, including macrophages, neutrophils, T cells, mast cells, epithelial cells, and mesenchymal cells [6]. Similar to MT-MMPs, ADAMs are transmembrane metalloproteinases, and are centrally implicated in ectodomain shedding of molecules such as cytokines, cytokine receptors and growth factors [7]. In inflammatory bowel disease (IBD) there is a marked upregulation of mucosal MMPs and other proteolytic enzymes [6]. MMPs contribute to mucosal lesions in IBD not only by their broad tissue-degrading actions on ECM substrates, but also by their recently investigated specific effects on non-matrix substrates, such as intercellular junctions, cytokines/chemokines and therapeutic antibodies (Table 13.1).

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Abbreviations

ADAM:

A Disintegrin and A Metalloproteinase-containing protease

CD:

Crohn’s disease

DSS:

dextran sodium sulfate

ECM:

extracellular matrix

IBD:

inflammatory bowel disease

Ig:

immunoglobulin

IL:

interleukin

JAM-A:

junctional adhesion molecule-A

MMP:

matrix metalloproteinase

MT:

membrane-bound

PGP:

proline–glycine–proline

TIMP:

tissue inhibitor of metalloproteinases

TNBS:

trinitrobenzene sulfonic acid

TNF:

tumor necrosis factor

UC:

ulcerative colitis

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Authors and Affiliations

  1. Centre for Immunobiology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT, UK

    Paolo Biancheri M.D., Ph.D. & Thomas T. MacDonald Ph.D., F.R.C.Path., F.Med.Sci.

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  1. Paolo Biancheri M.D., Ph.D.
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  2. Thomas T. MacDonald Ph.D., F.R.C.Path., F.Med.Sci.
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Correspondence to Thomas T. MacDonald Ph.D., F.R.C.Path., F.Med.Sci. .

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  1. Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Charité Medical School—Humboldt-University of Berlin, Berlin, Germany

    Daniel C. Baumgart

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Biancheri, P., MacDonald, T.T. (2017). Matrix Metalloproteinases. In: Baumgart, D. (eds) Crohn's Disease and Ulcerative Colitis. Springer, Cham. https://doi.org/10.1007/978-3-319-33703-6_13

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