TY - JOUR T1 - MMPs are regulatory enzymes in pathways of inflammatory disorders, tissue injury, malignancies and remodelling of the lung JF - European Respiratory Journal JO - Eur Respir J SP - 12 LP - 14 DO - 10.1183/09031936.00079311 VL - 38 IS - 1 AU - J. Müller-Quernheim Y1 - 2011/07/01 UR - http://erj.ersjournals.com/content/38/1/12.abstract N2 - Members of the matrix metalloproteinase (MMP) family of zinc-dependent proteolytic enzymes regulate physiological and pathophysiological events in development, injury and repair, such as morphogenesis, vasculogenesis, remodelling of the extracellular matrix, cell migration, cleavage of cytokines, and activation of mediators and defensins. They are synthesised as secreted or transmembrane proenzymes and processed to their active forms by the removal of amino-terminal propeptides. Their activation by the cleavage of the prodomain from the latent proenzyme and the presence of natural inhibitors, such as tissue inhibitors of metalloproteinases (TIMPs), are important mechanisms that restrict the action of secreted MMPs to the micromilieu of their origin. This tight control of activation and the redundant design of the MMP system, points to their importance in the named processes. In most tissues, their constitutive expression is low and their overexpression at sites of inflammation or other pathogenic events was thought to be due the classical role of extracellular matrix degradation.However, MMPs are no longer thought of as just matrix-degrading proteins. Rather, proteolysis should be viewed as an important post-translational principle of regulating a fast spectrum of biological processes, and the functional redundancy in combination with a wide substrate overlap underscores the pivotal roles of MMPs not only as effectors but also in regulatory mechanisms. Thus, MMPs are essential in many physiological events and the increasing interest in their function originates from their contribution to inflammatory and remodelling processes, in which they regulate physical barriers, release bioactive factors, participate in membrane shedding, modulate chemokine gradients that regulate leukocyte motility, activate cells via triggering of proteinase-activated receptors (PAR), and alter the activity status of other proteases, including other MMPs. Consequently, the majority of MMP substrates are non-matrix proteins, which underscores their critical roles in regulatory processes [1, 2]. Reports implicating MMPs in destructive pathogenic … ER -