The nonhematopoietic effects of erythropoietin in skin regeneration and repair: from basic research to clinical use

Med Res Rev. 2013 May;33(3):637-64. doi: 10.1002/med.21259. Epub 2012 Mar 19.

Abstract

Erythropoietin (EPO) is the main regulator of red blood cell production but there exists also a variety of nonhematopoietic properties. More recent data show that EPO is also associated with the protection of tissues suffering from ischemia and reperfusion injury as well as with improved regeneration in various organ systems, in particular the skin. This review highlights the mechanisms of EPO in the different stages of wound healing and the reparative processes in the skin emphasizing pathophysiological mechanisms and potential clinical applications. There is clear evidence that EPO effectively influences all wound-healing phases in a dose-dependent manner. This includes inflammation, tissue, and blood vessel formation as well as the remodeling of the wound. The molecular mechanism is predominantly based on an increased expression of the endothelial and inducible nitric oxide (NO) synthase with a consecutive rapid supply of NO as well as an increased content of vascular endothelial growth factor (VEGF) in the wound. The improved understanding of the functions and regulatory mechanisms of EPO in the context of wound-healing problems and ischemia/reperfusion injury, especially during flap surgery, may lead to new considerations of this growth hormone for its regular clinical application in patients.

Publication types

  • Review

MeSH terms

  • Animals
  • Epoetin Alfa
  • Erythropoietin / pharmacology*
  • Erythropoietin / therapeutic use
  • Humans
  • Neovascularization, Physiologic / drug effects
  • Nitric Oxide Synthase Type II
  • Recombinant Proteins / therapeutic use
  • Regeneration / drug effects
  • Reperfusion Injury
  • Skin / blood supply
  • Skin Physiological Phenomena / drug effects*
  • Surgical Flaps / physiology
  • Vascular Endothelial Growth Factor A / metabolism
  • Wound Healing / drug effects*
  • Wound Healing / physiology

Substances

  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Erythropoietin
  • Epoetin Alfa
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II