As part of our initiative to expand the scope of the Journal of Cellular Physiology, we are increasing our commitment to publish reviews that address timely issues with broad based relevance in rapidly moving fields. Matrix metalloproteinases (MMPs), the family of enzymes largely responsible for degradation of the extracellular matrix is an area of research that is generating increasing interest in the past several years. The first MMP (collagenase) was isolated from the tails of involuting tadpoles more than 40 years ago. Subsequently, more than 26 family members have been discovered, their varied substrates have been documented, and their functional roles in physiological control and in the pathogenesis of disease have been documented.
Low levels of MMPs contribute to physiological processes that include, but are not restricted to, reproduction, angiogenesis, and wound healing. In contrast, aberrantly high levels of MMPs are associated with and functionally linked to the pathogenesis of diseases that include arthritis, cancer, atherosclerosis and periodontitis. Thus, there is a dichotomy between physiologic and pathologic expression of these enzymes which suggests differences in their functional roles in biology and pathology.
Most MMPs are secreted into the extracellular space as latent enzymes that are activated proteolytically by serine proteinases or by other MMPs. However, one intriguing sub-group of MMPs is the MT-MMPs, membrane-anchored MMPs that are activated intracellularly by a furin-like mechanism and inserted into the membrane in an active form. The first membrane-bound form, MT1-MMP, was described about 10 years ago, and this sub-group now contains six members. Their membrane-bound location appears to confer unique characteristics. Consequently, interest in their structure and function, their pattern of expression and the mechanisms regulating their expression and activity continues to grow.
We hope that you share our enthusiasm for these two reviews on the expression and activity of MT1-MMP. We are committed to further addressing dimensions of matrix metalloproteinase control within a context of biological regulation and relevance to disease.