Matrix metalloproteinases: Structure and mechanisms of regulation

The extracellular matrix (ECM) is an highly dinamic structure and its remodeling represents an important physiological event during development and homeostasis as well as in a number of pathological processes including inflammation, autoimmunity and tumor growth and metastasis. In normal physiological condition ECM turnover is regulated by a balance in the levels of components synthesis and degradation. The family of matrix metalloproteinases (MMPs) represents one of the major groups of ECM-degrading enzyme which includes collagenases, stromelysins and gelatinases. The activity of these enzymes is thightly controlled by a family of tissue inhibitors of metalloproteinases (TIMPs) of which four members (TIMP-1, TIMP-2, TIMP-3, TIMP-4) have been characterized. The coordinate expression and activity of MMPs and TIMPs, required for a proper ECM turnover, has been reported in different cell types in response to different stimuli. The loss of coordinate TIMP and MMP expression and activity resulting in an increased ECM proteolysis has been proposed to underlie pathological conditions such as connective tissue disease and tumor invasion and metastasis. In the present report we have analyzed the structure and the function of the different components of the MMP family as well as the main mechanisms involved in the regulation of their activity.