Pathologies of MMP-2 underactivity: A perspective on a neglected condition

A member of the matrix metalloproteinase family, matrix metalloproteinase-2 (MMP-2, gelatinase A), has been extensively studied for its role in both normal physiology and pathological processes. Whereas most research efforts in recent years have investigated the pathologies associated with MMP-2 overactivity, the pathological mechanisms elicited by MMP-2 underactivity are less well understood. Here, we distinguish between two states and describe their causes: (i) MMP-2 deficiency (complete loss of MMP-2 activity) and (ii) MMP-2 insufficiency (defined as MMP-2 activity below baseline levels). Further, we review the biology of MMP-2, summarizing the current literature on MMP-2 underactivity in both mice and humans, and describe research being conducted by our lab towards improving our understanding of the pathological mechanisms elicited by MMP-2 deficiency / insufficiency. We think that this research could stimulate the discovery of new therapeutic approaches for managing pathologies associated with MMP-2 underactivity. Moreover, similar concepts could apply to other members of the matrix metalloproteinase family.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author