FOXO1 transcriptionally regulates GPX4 and protects renal tubule cells against cisplatin-mediated ferroptosis
Objective:To examine the potential transcriptional regulation of GPX3 by FOXO1 in order to protect renal tubular epithelial cells from cisplatin-induced ferroptosis.Methods:siRNA was utilized to create FOXO1 knockdown and the lentiviral vector was utilized to create FOXO1 overexpression in the human renal tubular epithelial cell line HK-2,with negative control.An acute kidney injury model of HK-2 cells was established through cisplatin(CP)induction.Chromatin immunoprecipitation and quantitative PCR(CHP-QPCR),double luciferase assay,malondialdehyde(MDA),Liperfluo staining,propyl iodide(PI)staining,and western blotting were employed to investigate the potential regulation of GPX4 expression by FOXO1,as well as its ability to mitigate CP-induced iron death in HK-2 cells.Results:FOXO1 binds to the GPX4 promoter region and modulates the expression of GPX4.Furthermore,overexpression of FOXO1 can effectively mitigate the peroxidation damage caused by CP.Conclusion:The findings suggest that FOXO1 may play a regulatory role in GPX4 expression,thereby reducing iron death in HK-2 cells induced by cisplatin.
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