title: Deferoxamine enhances neovascularization and accelerates wound healing in diabetic rats via the accumulation of hypoxia-inducible factor-1α.
abstract: OBJECTIVE
  Hypoxia-inducible factor (HIF)-1α plays a pivotal role during the process of wound healing. Previous studies reported that deferoxamine (DFO) could increase HIF-1α stability. This study aimed to investigate the effects of DFO on wound healing in diabetic rats and explore the underlying mechanism both in vivo and in vitro.
  
  
  METHODS
  An excisional diabetic wound model was established and the wound healing among vehicle control, DFO and vascular endothelial growth factor (VEGF) treatment groups was evaluated by macroscopy, histology and Western blot analysis. Human umbilical vein endothelial cells (HUVECs) were treated with DFO or HIF-1α siRNA, and then endothelial tube formation, cell proliferation and migration were examined.
  
  
  RESULTS
  DFO-treated wounds exhibited accelerated wound healing with enhanced granulation formation and increased re-epithelialization. Compared to the vehicle or VEGF treatment, DFO significantly increased neovascularization through up-regulation of HIF-1α and target genes including VEGF and stromal cell-derived factor-1α (SDF-1α). DFO failed to stimulate the expression of VEGF and SDF-1α in HUVECs depleted of HIF-1α. In addition, DFO promoted the angiogenic-associated processes of endothelial tube formation, cell proliferation and migration in HIF-1α dependent manner.
  
  
  CONCLUSIONS
  DFO enhances neovascularization and accelerates diabetic wound healing through the accumulation of HIF-1α and the regulation of endothelial cell function.
authors.affiliation: Department of Emergency Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Zhanjiang
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Department of Head and Neck Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Nie
authors.affiliation: Department of Emergency Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Si
authors.affiliation: Department of Orthopedic Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: yongshenma@163.com.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009389:Neovascularization, Pathologic; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017262:Siderophores / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D017262:Siderophores; D042461:Vascular Endothelial Growth Factor A; D003676:Deferoxamine