Matrix metalloproteinases in skin.
Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases collectively capable of degrading essentially all extracellular matrix components. These enzymes can be produced by several different types of cells in skin such as fibroblasts, keratinocytes, macrophages, endothelial cells, mast cells, and eosinophils and their activity can be specifically inhibited by TIMPs (tissue inhibitors of metalloproteinases), which bind to active MMPs with 1:1 stoichiometry. In general, MMPs are not constitutively expressed in skin but are induced temporarily in response to exogenous signals such as various cytokines, growth factors, cell matrix interactions and altered cell-cell contacts. At present, more evidence is accumulating that MMPs play an important role in proteolytic remodeling of extracellular matrix in various physiologic situations, including developmental tissue morphogenesis, tissue repair, and angiogenesis. On the other hand, MMPs play an important pathogenetic role in excessive breakdown of connective tissue components, e.g. in rheumatoid arthritis, osteoarthritis, chronic ulcers, dermal photoageing, and periodontitis, as well as in tumor cell invasion 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 expression of MMPs, on their substrate specificity, and MMP expression in physiologic and pathologic conditions of skin involving matrix remodeling. Furthermore, therapeutic modalities based on regulating MMP activity will be reviewed.
Kähäri
V M
VM
Department of Dermatology, Turku University Central Hospital, University of Turku, Finland.
Saarialho-Kere
U
U
D002280:Basal Cell Carcinoma / Q000201:enzymology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology; D005109:Extracellular Matrix / Q000201:enzymology*; D006801:Humans; D008545:Melanoma / Q000201:enzymology; D008666:Metalloendopeptidases / Q000502:physiology*; D012867:Skin / Q000201:enzymology*; D012871:Skin Diseases / Q000201:enzymology; D012878:Skin Neoplasms / Q000201:enzymology; D013379:Substrate Specificity; D019714:Tissue Inhibitor of Metalloproteinases / Q000502:physiology; D014945:Wound Healing
D019714:Tissue Inhibitor of Metalloproteinases; D008666:Metalloendopeptidases