Matrix-Metalloproteinasen bei chronisch-entzündlichen Darmerkrankungen – von der Grundlagenforschung zur klinischen Bedeutung

Zusammenfassung

Matrix-Metalloproteinasen (MMPs) sind zinkabhängige Endopeptidasen, die aufgrund ihres hohen proteolytischen Potenzials die wesentlichen Mediatoren des Umbaus der extrazellulären Matrix (ECM) darstellen. Neben der Fähigkeit, eine vollständige Degradation sämtlicher Metaboliten der ECM vorzunehmen, regulieren MMPs eine Vielzahl von Non-matrix-Substanzen, z. B. Chemokine, Zytokine oder Wachstumsfaktoren. Damit spielen MMPs eine entscheidende Rolle in zahlreichen physiologischen und pathologischen Prozessen wie Angiogenese, Wundheilung und Inflammation, einschließlich den mukosalen Entzündungsvorgängen bei chronisch entzündlichen Darmerkrankungen (CED). In jüngeren Studien konnte über die Mukosadestruktion hinaus eine Vielzahl weiterer Funktionen von MMPs in der Pathophysiologie des gesunden und inflammatorisch veränderten Darmes entschlüsselt werden. Der vorliegende Artikel gibt einen Überblick über die wesentlichen bei CED beteiligten MMPs, deren (patho)physiologische Relevanz sowie die klinischen Schlussfolgerungen, welche aus dem jeweiligen Expressions- und Regulationsverhalten der MMPs abgeleitet werden können.

Abstract

Matrix Metalloproteinases (MMPs) are a family of Zn^{2 +} -dependent endopeptidases that are considered to be the most potent proteases in the turnover of the extracellular matrix (ECM). In addition to their capability for degradating virtually all protein components of the ECM, MMPs regulate a variety of non-matrix substrates such as chemokines, cytokines and growth factors. Therefore MMPs play a central role in a variety of physiological and pathological processes such as angiogenesis, wound healing and inflammatory response including mucosal inflammation associated with inflammatory bowel disease (IBD). Apart from mucosal destruction in IBD, recent studies have identified several new functions of MMPs for the pathophysiology of the healthy and inflamed intestine. This article summarises the main activities of MMPs in IBD with emphasis on their pathophysiological relevance and potential clinical implications based on the expression and regulation patterns of these enzymes.

Schlüsselwörter

Colitis ulcerosa - Morbus Crohn - chronisch entzündliche Darmerkrankung - Matrix-Metalloproteinasen - TIMP

Key words

ulcerative colitis - Crohn’s disease - chronic inflammatory bowel disease - matrix metalloproteinases - TIMP

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