Roxadustat promotes angiogenesis through HIF‐1α/VEGF/VEGFR2 signaling and accelerates cutaneous wound healing in diabetic rats.
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 respons...
| Publicado en: | Wound Repair & Regeneration Vol. 27; no. 4; pp. 324 - 335 |
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| Autores principales: | , , , , |
| Formato: | pictorial research tables/charts Journal Article |
| Publicado: |
Wiley-Blackwell
Jul2019
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=137267790&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 137267790 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 10671927 DPV jtl: Wound Repair & Regeneration issn: 10671927 maglogo: Y pubinfo: dt: Jul2019 vid: 27 iid: 4 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 137267790 137267790 137267790 10.1111/wrr.12708 137267790 ppf: 324 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: Roxadustat promotes angiogenesis through HIF‐1α/VEGF/VEGFR2 signaling and accelerates cutaneous wound healing in diabetic rats. aug: au: Zhu, Yu Wang, Yanmao Jia, Yachao Xu, Jia Chai, Yimin affil: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Yishan Rd 600, Shanghai 200233 PR China sug: subj: Enzyme Inhibitors Pharmacodynamics Neovascularization, Physiologic Drug Effects DNA-Binding Proteins Drug Effects Vascular Endothelial Growth Factors Drug Effects Signal Transduction Drug Effects Wound Healing Drug Effects Skin Physiology Drug Effects Diabetes Mellitus Chemically Induced Animal Studies Rats Umbilical Veins Drug Effects Epithelium Drug Effects In Vivo Studies Biological Assay Methods Urea Adverse Effects ab: 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, roxadustat promotes angiogenesis via activation of the HIF‐1α/VEGF/VEGFR2 pathway and exhibits therapeutic effects on diabetic wound healing by increasing angiogenesis. Our findings suggest that roxadustat can be a promising strategy to promote diabetic cutaneous wound healing. pubtype: Academic Journal doctype: pictorial research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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