Developmental and homeostatic remodeling of the extracellular matrix (ECM) is a highly regulated process orchestrated by a
family of zinc-containing, calcium-dependent neutral proteases known as the matrix metallo-proteinases (MMP). This family
of enzymes, which now contains twenty members, can collectively degrade all structural proteins of the ECM including interstitial
collagens (I, II, III, and V), basement membrane collagens (IV), fibronectin, laminin, proteoglycan, and elastin (Table 1). The enzymatic activity of MMP family members is controlled by a group of inhibitor proteins known as the Tissue Inhibitors
of Metalloproteinases (TIMPs), which consist of four family members (Table 2). Whereas all four TIMPs can inhibit all MMPs in vitro, preferential TIMP-MMP interactions and tissue-restricted TIMP expression
suggest that each TIMP has a specific function (Table 2).
The Matrix Metalloproteinases (MMPs)
MMP family member
Collagens I, II, III, VI, X, gelatins, aggrecan, entactin
72 kDa Gelatinase, Gelatinase A
Gelatins, collagens I,IV, V, VII, X, XI, fibronectin, laminin, aggrecan, elastin, large tenascin C, vitronectin, β-amyloid
Aggrecan, gelatins, fibronectin, laminin, collagen III, IV, IX, X, large tenascin C, vitronectin
Aggrecan, fibronectin, laminin, collagen IV, elastin, entactin, small tenascin C, vitronectin
Collagenase-2, Neutrophil Collagenase
Collagens I, II, III, aggrecan
92 kDa Gelatinase, Gelatinase B
Gelatins, collagens IV, V, XIV, aggrecan, elastin, entactin, vitronectin
Aggrecan, fibronectin, laminin, collagen IV
Fibronectin, laminin, collagen IV, aggrecan, gelatins
Collagens I, II, III
Collagens I, II, III, fibronectin, laminin, vitronectin, proteoglycan,
Amelogenin (The major tooth enamel matrix protein)
Tissue Inhibitors of Metalloproteinases (TIMPs)
Inhibition of all known MMP family members. Associates with proMMP-9. Inhibits angiogenesis. Erythroid-potentiating actvity.
Inhibitions all known MMP family members. Associates with MT1-MMP and MMP-2 at cell surface and regulates MMP-2 activation.
Inhibition of all known MMP family members. Extracellular matrix-associated. Mutation associated with Sorsby's fundus dystrophy.
Inhibition of all known MMP family members. Restricted expression suggests tissue specific TIMP function.