Matrix turnover

In most adult tissues turnover of matrix is slow. There are, however, situations such as in embryonic and postnatal development, and in the postpartum uterus, where there is considerable tissue removal and replacement. The structural fibers, in general, have a longer half-life than the ground substance. In the case of elastin in aorta it has been suggested that, under normal circumstances, once laid down it lasts through life.

Resorption of matrix components is achieved by resident cells as well as infiltrating cells, such as neutrophils and macrophages. In general both extracellular and intracellular mechanisms are thought to play a part, although current thinking is that the initial step is an extracellular proteolytic cleavage.

Matrix macromolecules can be degraded by four classes of proteinases, and their relative roles in vivo may vary depending on the situation. The cysteine and aspartic proteinases function optimally at acid pH, and while there may be local acidic environments and some of the cysteine proteinases have been found extracellularly, they are probably major determinants of degradation of phagocytosed material. Circulating plasminogen activator and plasmin are key serine proteinases in regulation of turnover. The elastase and cathepsin G of polymorphonuclear leukocytes and the tryptase and chymase of mast cells, are all serine proteinases capable of matrix degradation.

The matrix metalloproteinases (MMPs) are a family of enzymes which bind metals, are secreted in an inactive form and require extracellular activation. There are at least nine members of the MMP gene family, which share extensive sequence homology, but differ in their substrate specificity (Table 3). Regulation of activity is determined intracellularly by transcriptional control, and extracellularly by activation and the presence of specific inhibitors. Inhibitors like <x,-macroglobulin bind and trap active enzymes; the tissue inhibitors of metalloproteinases (TIMPs) form noncovalent complexes with active

Table 3 Matrix metalloproteinase family

Enzyme

Mol. wt. (kDa)

Substrate

MMP1*

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