ABSTRACT
Matrix metalloproteinases (MMPs), also designated matnxms, are a family of related zinc metalloendopeptidases that function in the turnover of components of the extracellular matrix. These enzymes play a central role in the normal embryogenesis and tissue remodelling and in many diseases such as arthritis, cancer, periodontitis, glomerulonephritis, encephalomyelitis, atherosclerosis and tissue ulceration. The expression of matrixin genes is transcriptionally regulated by cytokines, growth factors, hormones, cellular transformation and a number of other cell mediators. Analyses of the promoter regions of the matrixin genes have revealed the presence of several regulatory elements. Matrixins are secreted as inactive proenzymes and the activation of these zymogens is one of the critical steps that leads to tissue catabolism. The latency of the proenzymes is associated with the interaction of a conserved cysteine in the propeptide with a zinc in the active site. MMP proenzymes are activated by proteinases, thiol-modifying reagents (mercurials, oxidized glutathione, HOCI), chaotropic agents and heat, treatments that result in the dissociation of the Cys-Zn interaction and the removal of the propeptide in a stepwise manner. Activated matrixins are inhibited by the endogenous protein inhibitors, tissue inhibitors of metalloproteinases (TIMPs), oc2-macroglobulin and its relatives. To date three TIMPs have been described and all bind to MMPs in a 1 : 1 molar stoichiometry. The expression of TIMP genes is also regulated by a number of factors. The balance between MMP and TIMP production thus governs the turnover of the extracellular matrix.
