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Induction and repression of collagenase-1 by keratinocytes is controlled by distinct components of different extracellular matrix compartments.

Abstract
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.
AuthorsB D Sudbeck, B K Pilcher, H G Welgus, W C Parks
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 272 Issue 35 Pg. 22103-10 (Aug 29 1997) ISSN: 0021-9258 [Print] United States
PMID9268353 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Collagen
  • Collagenases
  • Matrix Metalloproteinase 1
Topics
  • Cell Adhesion
  • Cell Compartmentation
  • Cells, Cultured
  • Collagen (metabolism)
  • Collagenases (biosynthesis, genetics, metabolism)
  • Enzyme Induction
  • Extracellular Matrix (metabolism)
  • Humans
  • Keratinocytes (enzymology)
  • Matrix Metalloproteinase 1
  • Promoter Regions, Genetic
  • Wound Healing

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