In all forms of cutaneous
wounds,
collagenase-1 (matrix metalloproteinase-1 (MMP-1)) is invariably expressed by basal keratinocytes migrating over the dermal matrix. We report that native
type I collagen mediates induction of MMP-1 by primary human keratinocytes.
Collagen-mediated induction of MMP-1 was rapid, being detected 2 h after plating, and was transcriptionally regulated. As demonstrated by in situ hybridization, only migrating keratinocytes expressed MMP-1, suggesting that contact with
collagen is not sufficient to induce MMP-1 expression in keratinocytes; the cells must also be migrating. Upon denaturation,
type I collagen lost its ability to induce MMP-1 expression but still supported cell adhesion. Other dermal or
wound matrix
proteins, such as
type III collagen,
fibrin, and
fibronectin, and a mixture of basement membrane
proteins did not induce MMP-1 production. In the presence of
collagen,
laminin-1 inhibited induction of MMP-1 but
laminin-5 did not. Taken together, these observations suggest that as basal keratinocytes migrate from the basal lamina onto the dermal matrix contact with native
type I collagen induces MMP-1 expression. In addition, our findings suggest that re-establishment of the basement membrane and, in particular, contact with
laminin-1 provides a potent signal to down-regulate MMP-1 production as the epithelium is repaired.