GHK-Cu-liposomes accelerate scald wound healing in mice by promoting cell proliferation and angiogenesis

Wound Repair Regen. 2017 Apr;25(2):270-278. doi: 10.1111/wrr.12520. Epub 2017 Apr 27.

Abstract

Glycyl-l-histidyl-l-lysine (GHK)-Cu is considered to be an activator of tissue remodeling, and has been used in cosmetic products. In this study, we prepared liposomes encapsulating GHK-Cu and analyzed their effect on human umbilical vein endothelial cells (HUVECs) proliferation and scald wound healing in mice. The nanoscaled GHK-Cu-liposomes promoted HUVECs proliferation, with a 33.1% increased rate. Flow cytometry analysis showed increased cell number at G1 stage and decreased cell number at G2 stage after GHK-Cu-liposomes treatment. Western blotting indicated that the expression of vascular endothelial growth factor and fibroblast grow factors-2 were both enhanced, as well as cell cycle-related proteins CDK4 and CyclinD1. In a mice scald model, angiogenesis in burned skin treated with GHK-Cu-liposomes was better compared with free GHK-Cu, and immunofluorescence analysis showed enhanced signal of CD31 and Ki67 in GHK-Cu-liposomes treated mice. Moreover, the wound healing time was shortened to 14 days post injury. Our results provide the evidence that GHK-Cu-liposomes could be utilized as a treatment for skin wounds.

MeSH terms

  • Animals
  • Blotting, Western
  • Burns / drug therapy*
  • Burns / metabolism
  • CDC2 Protein Kinase
  • Cell Proliferation / drug effects*
  • Cell Proliferation / physiology
  • Cyclin-Dependent Kinase 4
  • Disease Models, Animal
  • Fibroblast Growth Factors
  • Fibroblasts
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Liposomes
  • Mice
  • Neovascularization, Physiologic / drug effects*
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacology*
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / drug effects*
  • Wound Healing / physiology

Substances

  • Liposomes
  • Oligopeptides
  • Vascular Endothelial Growth Factor A
  • glycyl-histidyl-lysine
  • Fibroblast Growth Factors
  • CDC2 Protein Kinase
  • Cdk4 protein, mouse
  • Cyclin-Dependent Kinase 4