Matrix metalloproteinases (with accent to collagenases)

Abstract

Matrix metalloproteinases (MMPs) are a major group of enzymes that regulate cell–matrix composition. The MMPs are zinc-dependent endopeptidases known for their ability to cleave one or several extracellular matrix (ECM) constituents, as well as nonmatrix proteins. This review focuses on structural and functional elements of MMPs, and their roles in physiological and pathological processes, in which it is believed the MMPs play an important, or even indispensable role. According to their structural and functional characteristics, MMP family members have been classified into six different but closely related subgroups with fairly characteristic but often overlapping substrate specificities. MMP synthesis and functions are regulated by transcriptional activation, post-transcriptional processing (release of pro-domain, cell surface shedding), and control of activity by a family of endogenous inhibitors collectively known as tissue inhibitors of metalloproteinases (TIMPs). The balance of MMPs to TIMPs therefore determines matrix turnover, where either an excess of MMPs or a deficit of TIMPs may result in excess ECM degradation. Moreover, the recent development of selective and nonselective inhibitors of MMPs would also provide new insights in the knowledge of the relationship between activation of inflammatory cells and tissue remodeling and propose new therapeutic possibilities to the treatment of inflammatory disease.