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Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases, which are capable of collectively degrading all kinds of extracellular matrix proteins, but also can process a number of bioactive molecules.
Function
The MMPs play an important role in tissue remodeling associated with various physiological and pathological processes such as morphogenesis, angiogenesis, tissue repair, cirrhosis, arthritis and tumor invasion.
Classification
According to their cellular localization, the 28 human MMPs can be subdivided into secreted and membrane-bound MMPs. The membrane-bound MMPs include:
- The type-II transmembrane cysteine array MMP-23
- The glycosyl phosphatidylinositol-attached MMPs 17 and 25 / membrane-type MT-MMPs 4 and 6, and
- The type-I transmembrane MMPs 14, 15, 16, 24 / MT-MMPs 1, 2, 3, and 5.
In addition, some secreted MMPs such as (pro)MMP-2 are recruited to and activated at the cell surface to make focal proteolysis.
Inhibitors
The MMPs are inhibited by specific endogenous tissue inhibitor of metalloproteinases (TIMPs), which comprise a family of four protease inhibitors: TIMP-1, TIMP-2, TIMP-3 and TIMP-4. Overall, all MMPs are inhibited by TIMPs once they are activated but the gelatinases (MMP-2 and MMP-9) can form complexes with TIMPs when the enzymes are in the latent form. The complex of latent MMP-2 (pro-MMP-2)with TIMP-2 serves to facilitate the activation of pro-MMP-2 at the cell surface by MT1-MMP (MMP-14), a membrane-anchored MMP. The role of the pro-MMP-9/TIMP-1 complex is still unknown.
Pharmacology
Doxycycline, at subantimicrobial doses, inhibits MMP activity, and has been used in various experimental systems for this purpose.
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