Inhibition of miR200b Promotes Angiogenesis in Endothelial Cells by Activating The Notch Pathway

Objective Patients with diabetes mellitus frequently have chronic wounds or diabetic ulcers as a result of impaired wound healing, which may lead to limb amputation. Human umbilical vein endothelial cell (HUVEC) dysfunction also delays wound healing. Here, we investigated the mechanism of miR200b in HUVECs under high glucose conditions and the potential of miR200b as a therapeutic target.Materials and Methods In this experimental study, HUVECs were cultured with 5 or 30 mM glucose for 48 hours. Cell proliferation was evaluated by CCK8 assays. Cell mobility was tested by wound healing and Transwell assays. Angiogenesis was analyzed in vitro Matrigel tube formation assays. Luciferase reporter assays were used to test the binding of miR200b with Notch1.Results miR200b expression was induced by high glucose treatment of HUVECs (P 0.01), and it significantly repressed cell proliferation, migration, and tube formation (P 0.05). Notch1 was directly targeted and repressed by miR200b at both the mRNA and protein levels. Inhibition of miR200b restored Notch1 expression (P 0.05) and reactivated the Notch pathway. The effects of miR200b inhibition in HUVECs could be reversed by treatment with a Notch pathway inhibitor (P 0.05), indicating that the miR200b/Notch axis modulates the proliferation, migration, and tube formation ability of HUVECs.ConclusionInhibition of miR200b activated the angiogenic ability of endothelial cells and promoted wound healing through reactivation of the Notch pathway in vitro. miR200b could be a promising therapeutic target for treating HUVEC dysfunction.