Beneficial regulation of fibrillar collagens, heat shock protein-47, elastin fiber components, transforming growth factor-β1, vascular endothelial growth factor and oxidative stress effects by copper in dermal fibroblasts

Connect Tissue Res. 2012;53(5):373-8. doi: 10.3109/03008207.2012.665970. Epub 2012 Mar 15.


Skin aging is associated with the loss of the structural collagens and the elastin fiber components that form the extracellular matrix (ECM). It is associated with reduced transforming growth factor-β (TGF-β), angiogenesis and increased oxidative stress. Copper has been incorporated into cosmetics for anti-skin aging. This research investigated the mechanism for the anti-skin aging effect copper ions, from cuprous oxide powders. Dermal fibroblasts were exposed to copper and examined for expression (protein and/or promoter levels) of types I, III, V collagen, heat shock protein-47 (HSP-47), elastin, fibrillin-1, and fibrillin-2, TGF-β1, vascular endothelial growth factor (VEGF), and in addition for membrane damage and lipid peroxidation. The direct antioxidant activity of copper was also determined. The research indicates that copper's anti-skin aging and skin regeneration potential is through its stimulation of ECM proteins, TGF-β1, VEGF, and inhibition of oxidative stress effects at physiological concentrations; and supports its use in cosmetics.

MeSH terms

  • Cell Membrane / drug effects
  • Cell Membrane / pathology
  • Copper / pharmacology*
  • Dermis / cytology
  • Elastin / metabolism*
  • Fibrillar Collagens / metabolism*
  • Fibrillin-1
  • Fibrillin-2
  • Fibrillins
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • HSP47 Heat-Shock Proteins / metabolism*
  • Humans
  • Lipid Peroxidation / drug effects
  • Microfilament Proteins / metabolism
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Transforming Growth Factor beta1 / metabolism*
  • Vascular Endothelial Growth Factor A / metabolism*


  • FBN1 protein, human
  • FBN2 protein, human
  • Fibrillar Collagens
  • Fibrillin-1
  • Fibrillin-2
  • Fibrillins
  • HSP47 Heat-Shock Proteins
  • Microfilament Proteins
  • Reactive Oxygen Species
  • Transforming Growth Factor beta1
  • Vascular Endothelial Growth Factor A
  • Copper
  • Elastin