The regulation of connective tissue metalloproteinases by natural inhibitors

The family of matrix metalloproteinases have a fundamental role in the breakdown of connective tissue matrices in both physiological and pathological processes. The endogenous levels of the tissue inhibitors of metalloproteinases are a key determinant in the regulation of the activity of these enzymes. Current research on the mode of action of these inhibitors at the molecular level, aimed at their use as models for low molecular weight inhibitors, is outlined. Preliminary evidence for inhibitor deficiency in disease states and their potential use as therapeutic agents are summarised.