Table 1.
Mammalian matrix metalloproteinases: substrate specificities and role in wound healing
| Determined in | ||||
|---|---|---|---|---|
| Member | Substrates | Role in wound healing | Cell culture | In vivo, ex vivo |
| Collagenases | ||||
| MMP-1 (collagenase-1) | Collagen I, II, III, VII, and X; aggrecan; serpins; alpha2-macroglobulin; kallikrein; chymase | Promotes human keratinocyte migration on fibrillar collagen | X | X |
| Expressed by keratinocytes at their trailing membrane edge during wound healing | ||||
| Overexpression in keratinocytes delays reepithelialization | ||||
| MMP-8 (collagenase-2) | Collagen I, II, and III; aggrecan; serpins; 2-MG | Cleaves collagens, predominant collagenase in healing wounds | X | |
| MMP-13 (collagenase-3) | Collagen I, II, III, IV, IX, X, and XIV; gelatin; fibronectin; laminin; tenascin; aggrecan; fibrillin; serpins | Promotes reepithelialization indirectly by affecting wound contraction | X | |
| Gelatinases | ||||
| MMP-2 (gelatinase A) | Gelatin; collagen I, IV, V, VII, and X; laminin; aggrecan; fibronectin; tenascin | Accelerates cell migration | X | |
| MMP-9 (gelatinase B) | Gelatin; collagen I, III, IV, V and VII; aggrecan; elastin; fibrillin | Expressed by keratinocytes at the leading edge of the wound | X | X |
| Promotes cell migration and reepithelialization except in cornea | ||||
| Stromelysins | ||||
| MMP-3 (stromelysin −1) | Collagen IV, V, IX, and X; fibronectin; elastin; gelatin; aggrecan; nidogen; fibrillin; E-cadherin | Expressed by keratinocytes at the proximal proliferating population that supplies the leading edge during wound healing | X | X |
| Affects wound contraction | ||||
| MMP-10 (stromelysin-2) | Collagen IV, V, IX, and X; fibronectin; elastin; gelatin; laminin; aggrecan, nidogen; E-cadherin | Expressed by keratinocytes at the leading edge of the wound | X | |
| MMP-11 (stromelysin-3) | Serine protease inhibitors; 1-proteinase inhibitor | Unknown | ||
| Matrilysins | ||||
| MMP-7 (matrilysin) | Elastin; fibronectin; laminin; nidogen; collagen IV; tenascin; versican; 1-proteinase inhibitor; E-cadherin; tumor necrosis factor | Required for reepithelialization of mucosal wounds | X | X |
| Metalloelastases | ||||
| MMP-12 (metalloeslastase) | Collagen IV; gelatin; fibronectin; laminin; vitronectin; elastin; fibrillin; 1-proteinase inhibitor; apolipoprotein A | Macrophage specific (not expressed by epithelial cells) | ||
| Membrane-type MMPs | ||||
| MMP-14 (MT1-MMP) | Collagen I, II, and III; gelatin; fibronectin; laminin; vitronectin; aggrecan; tenascin; nidogen; perlecan; fibrillin; 1-proteinase inhibitor; alpha2-macroglobulin; fibrin | Promotes keratinocyte outgrowth, airway reepithelialization and cell migration | X | X |
| MMP-15 (MT2-MMP) | Fibronectin; laminin; aggrecan; tenascin; nidogen; perlecan | Unknown | ||
| MMP-16 (MT3-MMP) | Collagen III; fibronectin; gelatin; casein; laminin; alpha2-macroglobulin | Unknown | ||
| MMP-17 (MT4-MMP) | Fibrin; fibrinogen; tumor necrosis factor precursor | Unknown | ||
| MMP-24 (MT5-MMP) | Progelatinase A | Unknown | ||
| MMP-25 (MT6-MMP; leukolysin) | Gelatin | Unknown | ||
| Other MMPs | ||||
| MMP-19 (RASI-1) | Gelatin; aggrecan; cartilage oligomeric matrix protein; collagen IV; laminin; nidogen; large tenascin | Unknown | ||
| MMP-20 (enamelysin) | Amelogenin; aggrecan; cartilage oligomeric matrix protein | Expressed in developing teeth | ||
| MMP-21 | Unknown | |||
| MMP-22 | Unknown | |||
| MMP-23 (CA-MMP) | Unknown | |||
| MMP-26 (endometase) | Expressed by migrating keratinocytes during cutaneous wound healing | |||
| MMP-27 | Unknown | |||
| MMP-28 (epilysin) | Casein | Expressed by a distal intact population of keratinocytes during wound healing | ||