MATRIX METALLOPROTEINASES IN SKIN

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endope ptidases collectively capable of degrading essentially all extracellul ar matrix components. These enzymes can be produced by several differe nt types of cells in skin such as fibroblasts, keratinocytes, macropha ges, endothelial cells, mast cells, and eosinophils and their activity can be specifically inhibited by TIMPs (tissue inhibitors of metallop roteinases), which bind to active MMPs with 1:1 stoichiometry. In gene ral, MMPs are not constitutively expressed in skin but are induced tem porarily in response to exogenous signals such as various cytokines, g rowth factors, cell-matrix interactions and altered cell-cell contacts . At present, more evidence is accumulating that MMPs play an importan t role in proteolytic remodeling of extracellular matrix in various ph ysiologic situations, including developmental tissue morphogenesis, ti ssue repair, and angiogenesis. On the other hand, MMPs play an importa nt pathogenetic role in excessive breakdown of connective tissue compo nents, e.g. in rheumatoid arthritis, osteoarthritis, chronic ulcers, d ermal photoageing, and periodontitis, as well as in tumor cell invasio n and metastasis. In this review we discuss the role of MMPs and TIMPs in human skin based on new observations on the regulation of the expr ession of MMPs, on their substrate specificity, and MMP expression in physiologic and pathologic conditions of skin involving matrix remodel ing. Furthermore, therapeutic modalities based on regulating MMP activ ity will be reviewed.