Abstract
BACKGROUND: Forkhead box K1 (FOXK1) is a newly discovered gene encoding a transcription factor in the FOX family. It plays important roles in the cell cycle, cell growth, proliferation, differentiation, apoptosis, metabolism, DNA damage, drug resistance, angiogenesis, and carcinogenesis by binding to DNA to function as a transcription factor. Many studies have confirmed that FOXK1 plays a role in promoting cancer in a variety of tumors. However, the pathogenic role of FOXK1 in diabetic retinopathy (DR) is still unclear. The present study was conducted to investigate the mechanism of FOXK1 in the vascular endothelial dysfunction of DR. METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to high glucose (HG) concentrations (25 mmol/L) to establish a vascular endothelial dysfunction model of DR. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the differential expression of FOXK1 in HUVECs treated with HG and low glucose (LG). CCK-8, Transwell, flow cytometry and tube formation assays were used to investigate the effect of FOXK1 on HUVECs function. To explore the downstream signaling pathway of FOXK1, Western blotting was subsequently used to detect the protein expression of p-AKT and AKT after FOXK1 was knocked down in HUVECs. The AKT inhibitor MK-2206 was used to treat HUVECs, and cell migration, apoptosis and angiogenesis were observed. RESULTS: The results showed that FOXK1 expression was significantly increased in HUVECs cultured with high glucose. In this endothelial dysfunction model, knockdown of FOXK1 increased HUVECs activity and migration, inhibited HUVECs apoptosis, angiogenesis and VEGF expression, and activated the p-AKT/AKT signaling pathway. All of these were reversed by the AKT inhibitor MK-2206. CONCLUSIONS: FOXK1 may mediate vascular endothelial dysfunction in DR by inhibiting p-AKT/AKT pathway.