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.

Abstract

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

Substances

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