Pro‐angiogenic role of ZEB1 in skin wound healing by upregulating VEGFA via microRNA‐206 suppression

Abstract

Angiogenesis has been identified to assume a critical role in skin wound healing. Moreover, zinc finger E‐box binding homeobox 1 (ZEB1) was capable of promoting skin wound healing. Herein, cell and animal experiments were implemented in this study to figure out whether ZEB1 orchestrated angiogenesis during skin wound healing. Subsequent to gain‐ and loss‐of‐function approaches in human dermal microvascular endothelial cells (HDMECs), HDMEC proliferation, migration and angiogenesis were evaluated by CCK8, EdU, wound healing, Transwell and angiogenesis in vitro assays. The relationship among ZEB1, microRNA (miR)‐206 and vascular endothelial growth factor A (VEGFA) was assessed by microarray analysis, dual‐luciferase, ChIP and RIP assays. Finally, the mechanism of ZEB1 in skin wound healing was confirmed by in vivo experiments. Mechanically, ZEB1 upregulation resulted in miR‐206 downregulation by binding to miR‐206 promoter, and miR‐206 repressed VEGFA expression by directly targeting. ZEB1 overexpression enhanced HDMEC proliferation, migration and angiogenesis, which was neutralized by miR‐206 upregulation or VEGFA inhibition. Moreover, ZEB1 significantly promoted skin wound healing in mice, which was negated by overexpression of miR‐206. Conclusively, ZEB1 augmented angiogenesis to promote skin wound healing by elevating VEGFA expression via miR‐206 repression.