Impaired keratinocyte function on matrix metalloproteinase-1 (MMP-1) damaged collagen

Arch Dermatol Res. 2009 Aug;301(7):497-506. doi: 10.1007/s00403-009-0948-4. Epub 2009 Apr 8.


Healing of superficial skin wounds depends on the proliferation and migration of keratinocytes at the wound margin. When human epidermal keratinocytes were incubated on polymerized type I collagen, they rapidly attached and spread. The cells underwent a proliferative response and, over the subsequent 6-day period, covered the collagen surface with a monolayer of cells. When keratinocytes were plated on collagen that had been fragmented by exposure to matrix metalloproteinase-1 (MMP-1, collagenase-1), the cells attached as readily as to intact collagen but spread more slowly and less completely. Growth was reduced by approximately 50%. Instead of covering the collagen surface, the keratinocytes remained localized to the site of attachment. Keratinocytes on fragmented collagen expressed a more differentiated phenotype as indicated by a higher level of surface E-cadherin. Based on these findings, we suggest that damage to the underlying collagenous matrix may impede efficient keratinocyte function and retard wound closure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cadherins / biosynthesis
  • Cadherins / genetics
  • Cell Adhesion / drug effects
  • Cell Differentiation
  • Cell Growth Processes / drug effects
  • Cell Movement / drug effects
  • Cells, Cultured
  • Collagen Type I / metabolism*
  • Collagenases / metabolism
  • Collagenases / pharmacology
  • Cytoskeleton
  • Epidermis / drug effects
  • Epidermis / metabolism*
  • Epidermis / pathology
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Keratinocytes / pathology
  • Matrix Metalloproteinase 1 / metabolism*
  • Matrix Metalloproteinase 1 / pharmacology
  • Polymers / metabolism*
  • Wound Healing / drug effects


  • Cadherins
  • Collagen Type I
  • Polymers
  • Collagenases
  • collagenase 1
  • Matrix Metalloproteinase 1