Matrix metalloproteinases and the regulation of tissue remodelling

Abstract

Matrix metalloproteinases (MMPs) were discovered because of their role in amphibian metamorphosis, yet they have attracted more attention because of their roles in disease. Recent work has highlighted the diverse consequences of MMP proteolysis on normal and pathological cell behaviour. Mutations in mouse MMP genes have displayed phenotypes in normal skeletal, mammary and vascular development. Drosophila melanogaster has only two MMP genes; mutations in both MMP genes have been isolated. Each mutant is larval lethal with defects in tissue remodelling. Collectively, the loss-of-function studies in different organisms point to MMPs as mediators of change and physical adaptation in tissues, whether developmentally regulated, environmentally induced or associated with disease. An important outstanding question is whether MMPs function primarily as structural effectors of tissue remodelling or as regulators of signalling networks. In this Review, we synthesize the current genetic evidence from mice, flies and humans on the normal functions of MMPs in embryonic and postnatal development. We highlight the consequences of modifying MMP action in D. melanogaster larval development, mammalian skeletal, vascular and mammary development and in inflammation and wound repair.