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(Received for publication, April 18, 1997, and in revised form, June 5, 1997)
From the Departments of 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.
Volume 272, Number 35,
Issue of August 29, 1997
pp. 22103-22110
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
and
¶
Medicine (Dermatology) and
¶ Cell Biology and Physiology, Washington University School of
Medicine, St. Louis, Missouri 63110
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