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Open AccessJournal Article

Activation mechanisms of matrix metalloproteinases.

Hideaki Nagase
- 01 Mar 1997 - 
- Vol. 378, pp 151-160
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TLDR
Recent progress made to elucidate the activation mechanisms of pro-matrixins are described which include extracellular stepwise activation common to most proMMPs, cell surface activation of progelatinase A and procollagenase 3, and intracellular activation of prostromelysin 3 and pro-membrane-type-1 MMP.
Abstract
Matrix metalloproteinases (MMPs), also called matrixins, function in the turnover of extracellular matrix components. These enzymes are considered to play important roles in embryo development, morphogenesis and tissue remodeling, and in diseases such as arthritis, periodontitis, glomerulonephritis, atherosclerosis, tissue ulceration, and in cancer cell invasion and metastasis. All MMPs are synthesized as preproenzymes and most of them are secreted from the cells as proenzymes. Thus, the activation of these proenzymes is one of the critical steps that leads to extracellular matrix breakdown. This review describes recent progress made to elucidate the activation mechanisms of pro-matrixins which include extracellular stepwise activation common to most proMMPs, cell surface activation of progelatinase A and procollagenase 3, and intracellular activation of prostromelysin 3 and pro-membrane-type-1 MMP.

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Metalloproteinase inhibitors: biological actions and therapeutic opportunities.

TL;DR: The concept of the use of the natural inhibitors, such as the TIMPs, in gene based therapies is being assessed in animal models and should provide useful insights into the cell biology of degradative diseases.
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