Matrix metalloproteinases: What do they not do? New substrates being identified
Numerous reports have shown that Matrix metalloproteinases(MMPs) are directly implicated in almost every biological process involving matrix remodeling throughout the mammalian life span, from embryo implantation to cell death or necrosis. But at what level is their role? For instance, MMP-driven proteolysis has been linked to several morphogenetic events during development, including mammary gland ductal branching, bone ossification and blood vessel remodeling. As well, MMPs play a primary role in normal tissue maintenance functions, including wound healing and repair, menstruation and reproductive processes, and innate immune defense. As a consequence, altered expression and/or misregulation of MMP activities in vivo has been associated with the development of a wide range of pathologies, including chronic inflammatory diseases and cancer. In all these functions, the conventional dogma still insists that MMPs participate in these pleiotropic functions primarily through degradation of the ECM.