Enhancing skin flap survival by a cell-permeable wild-type survivin.
Skin grafts, including skin flaps, are widely used in plastic and reconstructive surgery to cover wounds and tissue defects resulting from mechanic or burn injury. Ischemic necrosis is the main complication in skin graft surgery due to inefficient revascularization. Though the surgical delay procedure has been proved to be the only effective technique to prevent skin flap ischemic necrosis by mechanism of inducing adaption to hypoxia, but it is time consuming, costly, and having high risk of infection due to repeated surgery. Recent research demonstrated that, in addition to protecting cells against apoptosis, the expression of survivin correlates with intratumoral microvessel density in several different types of tumors and survivin could upregulate several proangiogenic factors, including VEGF, Egr-1 and Siah-1. Moreover, Survivin DeltaEx3, one of the survivin alternative splice variants, is necessary for activating the small GTPase Rac1 during endothelial tube formation and required for in vivo endothelial cell invasion. Therefore, we postulate that intracellular delivery of survivin or Survivin DeltaEx3 by fusion with protein transduction domain would enhance skin flap survival through accelerating revascularization by both inhibiting the apoptosis of microvascular endothelial cells and promoting skin flap angiogenesis. If the hypothesis was proved to be practical, the fusion proteins would be widely used in plastic and reconstructive surgery to prevent skin flap from ischemic necrosis in the future.
Shu
Mao-Guo
MG
Institute of Plastic Surgery, Xijing Hospital, The Fourth Military Medical University, No. 17 Changle Western Road, Xi'an 710032, P R China.
Guo
Xiao-Tong
XT
Zhen
Hai-Ning
HN
Han
Yan
Y
Chen
Fu-Lin
FL
Li
Li-Wen
LW
Guo
Shu-Zhong
SZ
D002463:Cell Membrane Permeability / Q000502:physiology*; D006085:Graft Survival; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000502:physiology*; D018919:Neovascularization, Physiologic; D012867:Skin / Q000098:blood supply; D016038:Skin Transplantation / Q000502:physiology*; D013524:Surgical Flaps; D000077022:Survivin
C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D000077022:Survivin