Roxadustat promotes angiogenesis through HIF-1α/VEGF/VEGFR2 signaling and accelerates cutaneous wound healing in diabetic rats.

Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society
Yu ZhuYimin Chai

Abstract

Diabetic foot ulcers are a major health-care burden worldwide. One primary cause of the delayed wound healing in diabetic patients is impaired function of the hypoxia-inducible factor-1α/vascular endothelial growth factor (HIF-1α/VEGF) axis, which results in compromised neovascularization in response to hypoxia. In the present study, we aimed to investigate the effect of roxadustat, a novel HIF prolyl-4-hydroxylase inhibitor, on angiogenesis and its therapeutic effect on cutaneous wound healing in diabetic rats. In vitro, we found that roxadustat could promote the angiogenic activity of human umbilical vein endothelial cells, accompanied by up-regulation of HIF-1α/VEGF/VEGFR2 signaling. Next, we demonstrated that Ki8751, a VEGFR2-specific inhibitor, could inhibit the increased angiogenic activity of human umbilical vein endothelial cells induced by roxadustat. In vivo, we performed a Matrigel plug assay and demonstrated that roxadustat induced vascularization of the Matrigel plugs, and this effect could be partially inhibited by Ki8751. Finally, we utilized a streptozotocin-induced diabetic rat model and found that roxadustat could accelerate cutaneous wound healing and promote angiogenesis in the wound sites. In conclusion, ro...Continue Reading

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Citations

Apr 28, 2020·Circulation Journal : Official Journal of the Japanese Circulation Society·Koji OhashiToyoaki Murohara
Jan 27, 2021·Diabetologia·Sergiu-Bogdan Catrina, Xiaowei Zheng
Jan 19, 2021·Evidence-based Complementary and Alternative Medicine : ECAM·Qiuyue GuoYanqin Huang
Apr 10, 2021·ACS Biomaterials Science & Engineering·Yuhang FuXiaoqin Wang
Apr 19, 2021·Pediatrics and Neonatology·Liang-Ti HuangChung-Ming Chen
Sep 28, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Victoria H KoMark Puder
Dec 8, 2021·Expert Opinion on Therapeutic Targets·Jonathan Golledge, Shivshankar Thanigaimani
Jul 4, 2020·Current Diabetes Reviews·Kuldeep B PawarAtul A Deshmukh
Jan 9, 2022·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Gui WanZhenbing Chen

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