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Volume 272, Number 35, Issue of August 29, 1997 pp. 22103-22110
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Induction and Repression of Collagenase-1 by Keratinocytes Is Controlled by Distinct Components of Different Extracellular Matrix Compartments

(Received for publication, April 18, 1997, and in revised form, June 5, 1997)

Barry D. Sudbeck Dagger , Brian K. Pilcher Dagger , Howard G. Welgus Dagger and William C. Parks Dagger

From the Departments of Dagger  Medicine (Dermatology) and  Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110

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.


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