Background
Hyperglycemia, a characteristic feature of diabetes, induces vascular complications by accelerating endothelial cell (EC) apoptosis and limiting their proliferation. The potential role of Forkhead box M1 (FoxM1) in high glucose (HG)-induced EC injury remains largely unknown. We aimed to investigate the role and underlying mechanism of FoxM1 in regulating EC injury. Material and
Conclusion
FoxM1 protects ECs from HG-induced growth arrest and cell apoptosis by suppressing ROS caused by the regulation of Akt and ERK pathways, which can aid in developing new therapeutic strategies for the treatment of EC dysfunction.
Material and methods
Human umbilical vein endothelial cells (HUVECs) were treated with various concentrations of glucose (5.5, 15, 30 and 50 mM). The expression of FoxM1 was determined via qPCR and western blotting. Overexpression of FoxM1 was achieved by transfection with FoxM1 overexpression plasmid. Reactive oxygen species (ROS) production, cell apoptotic rates, and cell cycle analysis were detected by flow cytometry, and cell proliferation was measured by CCK8 assay.
Methods
Human umbilical vein endothelial cells (HUVECs) were treated with various concentrations of glucose (5.5, 15, 30 and 50 mM). The expression of FoxM1 was determined via qPCR and western blotting. Overexpression of FoxM1 was achieved by transfection with FoxM1 overexpression plasmid. Reactive oxygen species (ROS) production, cell apoptotic rates, and cell cycle analysis were detected by flow cytometry, and cell proliferation was measured by CCK8 assay.
Results
The expression level of FoxM1 was downregulated in HUVECs under HG condition when compared to cells with normal glucose. HG treatment induced overproduction of ROS and subsequent apoptosis. However, FoxM1 overexpression of FoxM1 reduced the levels of ROS and inhibited apoptosis. In addition, HG induced impairment of cell proliferation and caused cell cycle arrest in the G0/G1 phrase. Contrarily, FoxM1 overexpression promoted cell proliferation and alleviated G0/G1 cell cycle arrest caused by HG stimulation. Moreover, treatment with HG reduced phosphorylation of the Akt and ERK signaling pathways, and this was remarkably reversed by FoxM1 overexpression.