Stimulation of cell proliferation and expression of matrixmetalloproteinase-1 and interluekin-8 genes in dermal fibroblasts by copper

Connect Tissue Res. 2010 Jun;51(3):224-9. doi: 10.3109/03008200903288431.


Copper is essential to wound healing as well as a widespread environmental pollutant, with skin aging potential. Wound healing and skin aging are facilitated by matrixmetalloproteinases (MMP), which remodel the extracellular matrix, and interleukin-8 (IL-8), linked with copper. This research investigated the mechanism to copper's role in wound healing or skin aging by regulation of MMP-1 and IL-8 genes. It examined the dose-responsive effects of copper on MMP-1, -2, and -9 activities; MMP-1 and IL-8 gene regulation at protein, mRNA, and promoter levels; tissue inhibitor of matrixmetalloproteinases-1 (TIMP-1) expression; and cell proliferation. Copper stimulated cell proliferation and the expression of MMP-1 and IL-8 genes at the protein, mRNA, and promoter levels, indicating transcriptional regulation, without significantly altering TIMP-1. The research suggests that copper facilitates wound healing as well as skin aging via the induction of MMP-1 expression, with limiting MMP effect at the higher concentrations through enhanced IL-8 expression, which favors extracellular matrix deposition.

MeSH terms

  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Copper / pharmacology*
  • Environmental Pollutants / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Gene Expression / drug effects
  • Humans
  • Infant, Newborn
  • Interleukin-8 / genetics*
  • Interleukin-8 / metabolism
  • Matrix Metalloproteinase 1 / genetics*
  • Matrix Metalloproteinase 1 / metabolism
  • RNA, Messenger / metabolism
  • Skin / drug effects*
  • Skin / metabolism
  • Skin Aging / drug effects
  • Skin Aging / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Wound Healing / drug effects
  • Wound Healing / genetics


  • Environmental Pollutants
  • Interleukin-8
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Copper
  • Matrix Metalloproteinase 1