Augmentation of hypoxia-inducible factor-1-alpha in reinfused blood cells enhances diabetic ischemic wound closure in mice
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Huan Wang1,*, Yufeng Feng2,*, Xiaoju Jin3, Rong Xia4, Yong Cheng1, Xiaoqian Liu1, Nana Zhu1, Xun Zhou1, Lei Yin1 and Jianrong Guo1
1Department of Anesthesiology, Gongli Hospital, The Second Military Medical University, Shanghai 200135, China
2Department of Anesthesiology, The First Affiliated Hospital of Xiamen University, Xiamen 361003, China
3Department of Anesthesiology, Yijishan Hospital Affiliated to Wannan Medical College, Wuhu 241001, China
4Transfusion Department, Huashan Hospital, Fudan University, Shanghai 200040, China
Jianrong Guo, email: [email protected]
Keywords: diabetic wound closure; blood re-infusion; hypoxia-inducible factor-1a (HIF-1a); vascular endothelial growth factor (VEGF)
Received: June 27, 2017 Accepted: August 04, 2017 Published: December 13, 2017
Diabetes-associated dysfunction in angiogenesis predominantly contributes to impairment of wound closure, but a role of hypoxia-inducible factor 1 alpha (HIF-1a) in the process remain poorly understood. Here, we examined whether expression of HIF-1a in re-infused blood cells may improve the diabetic wound closure in mice. We found that that expression of HIF-1a in re-infused isogeneic blood cells significantly improved diabetic wound healing in mice, seemingly through augmentation of wound-associated angiogenesis. Mechanistically, expression of HIF-1a in re-infused blood cells significantly increased macrophage infiltration at the wound site, and macrophages produced vascular endothelial growth factor A (VEGF-A) to promote wound-associated angiogenesis. Together, our data suggest that augmentation of HIF-1a in reinfused blood cells may enhance diabetic ischemic wound closure.
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