Copper-GHK increases integrin expression and p63 positivity by keratinocytes

Arch Dermatol Res. 2009 Apr;301(4):301-6. doi: 10.1007/s00403-009-0942-x. Epub 2009 Mar 25.

Abstract

Glycyl-L-histidyl-L-lysyl (GHK) possesses a high affinity for copper(II) ions, with which it spontaneously forms a complex (copper-GHK). It is well known that copper-GHK plays a physiological role in the process of wound healing and tissue repair by stimulating collagen synthesis in fibroblasts. This study was conducted to investigate the effects of copper-GHK on keratinocytes. Proliferative effects were analyzed and hematoxylin and eosin staining and immunohistochemistry were conducted to evaluate the effects of copper-GHK in skin equivalent (SE) models. In addition, western blotting was performed. In monolayer cultured keratinocytes, copper-GHK increased the proliferation of keratinocytes. When the SE models were evaluated, basal cells became cuboidal when copper-GHK was added. Immunohistochemical analysis revealed that copper-GHK increased proliferating cell nuclear antigen (PCNA) and p63 positivity. Furthermore, the expression of integrin alpha6 and beta1 increased in SE models, and these results were confirmed by Western blotting. The results of this study indicate that treatment with copper-GHK may increase the proliferative potential of basal keratinocytes by modulating the expression of integrins, p63 and PCNA. In addition, increased levels of p63, a putative stem cell marker of the skin, suggests that copper-GHK promotes the survival of basal stem cells in the skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / drug effects
  • Copper / chemistry*
  • Copper / metabolism
  • Foreskin / cytology
  • Humans
  • Infant, Newborn
  • Integrin alpha6 / genetics
  • Integrin alpha6 / metabolism*
  • Integrin beta1 / genetics
  • Integrin beta1 / metabolism*
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Oligopeptides / metabolism*
  • Organ Culture Techniques
  • Organometallic Compounds / pharmacology*
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / metabolism
  • Protein Binding
  • Protein Conformation
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Up-Regulation

Substances

  • CKAP4 protein, human
  • Integrin alpha6
  • Integrin beta1
  • Membrane Proteins
  • Oligopeptides
  • Organometallic Compounds
  • Proliferating Cell Nuclear Antigen
  • Tumor Suppressor Protein p53
  • Copper