Matrix Metalloproteinases (MMPs)
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Introduction
Matrix metalloproteinases (MMPs) are a group of zinc-dependent endopeptidases that are responsible for the degradation of extracellular matrix components, secreted by many cells such as fibroblasts, vascular smooth muscle (VSM), and leukocytesand. They play a crucial role in various physiological and pathologic processes. MMPs consist of a propeptide sequence of about 80 amino acids, a catalytic metalloproteinase domain with catalytic zinc of about 170 amino acids, a hinge region or linker peptide of variable length, and a hemopexin domain of about 200 amino acids. In vertebrates, the MMP family comprises 28 members, at least 23 in human tissues, and 14 of which are expressed in the vasculature. Typically, MMPs are classified according to their substrates and the organization of their structural domains into collagenases, gelatinases, stromelysins, matrilysins, membrane-type (MT)-MMPs, and other MMPs.
Mechanism of action
MMPs are regulated in terms of mRNA expression level and by activation of their latent zymogen form. MMPs are often secreted as inactive form which is cleaved to the active form by various proteinases including other MMPs. MMPs are involved in degradation of ECM proteins such as collagen and elastin, but could influence endothelial cell function as well as VSM cell migration, proliferation, Ca2+ signaling and contraction. MMPs promote cell proliferation, migration, and differentiation, thus playing a role in cell apoptosis, tissue repair, immune response and angiogenesis. MMPs may also affect bioactive molecules on the cell surface and modulate various cellular and signaling pathways.
Application of MMPs
MMPs are associated with different physiological responses, including embryogenesis, vasculogenesis, and cellular remodeling, as well as different disease pathogenesis. MMPs have been proposed as biomarkers for numerous pathological conditions and are potential therapeutic targets in cardiovascular diseases such as atherosclerosis, varicose veins, aneurysms, musculoskeletal disorders such as osteoarthritis and bone resorption, and in various cancers. The imbalance between the expression of MMPs and their inhibitors can be also effective in leukemic cell processes such as migration, angiogenesis, survival, and apoptosis, playing a key role in the progression and prognosis of leukemia.
References
- Kasturi Chatter., jeeSayantan Jana., Preety Choudhary.,&Snehasikta Swarnakar. (2018).Triumph and tumult of matrix metalloproteinases and their crosstalk with eicosanoids in cancer. Cancer and Metastasis Reviews , 37(2-3), 279-288.
- Ning Cui., Min Hu., Raouf A. Khalil. (2017). Biochemical and Biological Attributes of Matrix Metalloproteinases. Prog Mol Biol Transl Sci , 147, 1-73.
