MMPmediated

MMP-mediated refers to biological processes driven by matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases that degrade components of the extracellular matrix (ECM) and other extracellular substrates. MMPs are synthesized as inactive proenzymes and become active through proteolytic removal of their propeptide. Their activity is tightly controlled by tissue inhibitors of metalloproteinases (TIMPs) and by their cellular localization and activation status.

In physiology, MMP-mediated remodeling supports embryonic development, wound repair, angiogenesis, and tissue turnover. In pathology, aberrant MMP activity can promote disease progression, notably cancer invasion and metastasis through degradation of basement membranes and ECM, as well as angiogenic remodeling; there are also roles in osteoarthritis, rheumatoid arthritis, atherosclerosis, chronic obstructive pulmonary disease, and periodontitis.

MMP substrates extend beyond structural ECM proteins such as collagens, gelatin, laminin, and proteoglycans to include non-matrix targets like cytokines, growth factors, and cell-surface receptors. Key enzymes include MMP-2 and MMP-9, gelatinases that degrade type IV collagen in basement membranes; MT1-MMP (MMP-14), a membrane-anchored MMP that activates other MMPs and remodels pericellular matrix; and MMP-3 (stromelysin) which can activate pro-MMPs.

Regulation of MMP-mediated processes involves transcriptional control, zymogen activation, TIMP-mediated inhibition, and spatial confinement within tissue compartments. Clinically, broad MMP inhibitors have faced challenges due to limited selectivity and adverse effects, though MMP activity remains a focus as a biomarker and therapeutic target, with ongoing research using activity assays, imaging probes, and genetic models. See also extracellular matrix, TIMPs, proteolysis.