Role of metalloproteinases in epithelial repair

Different members of the matrix metalloproteinases family facilitate re-epithelialization by acting on specific substrates. In skin, collagenase-1 (MMP-1) is induced in migrating keratinocytes by ligation of the α2β1 integrin with dermal type I collagen. Once cleaved by MMP-1, the collagen helix relaxes, and α2β1 dislodges and establishes new contacts with intact collagen in the open wound bed. Thus, the activity of MMP-1 facilitates wound closure by altering the affinity of integrin–collagen interactions. In mucosal tissues, wound-edge epithelial cells express matrilysin (MMP-7)—which is not produced in skin. Wounds in the lung and gut of matrilysin-deficient animals show markedly impaired re-epithelialization. Ultrastructural and biochemical observations indicate that in the absence of matrilysin, adherens junctions are not remodel and E-cadherin is not shed, thereby impairing migration by hindering the rear-release of cells at the migrating edge. Our findings demonstrate that MMP-1 and MMP-7 mediate essential processes of re-epithelialization in different tissues.