海南医科大学学报2025，Vol.31Issue(9)：667-674,8.DOI:10.13210/j.cnki.jhmu.20250114.001
醉茄素A抑制肾近端小管上皮细胞铁死亡
Withaferin A attenuates ferroptosis in renal proximal tubule epithelial cells
摘要
Abstract
Objective:To investigate the effect of Withaferin A on the death of renal proximal tubule epithelial cells induced by cisplatin and underlying molecular mechanism.Methods:The cytotoxicity of cisplatin and Withaferin A was analyzed using the CCK-8 cell activity assay.BODIPY 581/591 C11 was used to stain cells,and lipid ROS content was detected by flow cytometry.The expression of ferroptosis-related genes in HK-2 cells and primary cells treated with cisplatin and Withaferin A was analyzed by RT-PCR array assays.The expression of FSP1 was detected by Western Blot.By small RNA(siRNA)interfering,the expres-sion of FSP1 gene was depleted in cells.Results:Withaferin A was found to inhibit cisplatin-induced toxicity in renal proximal tu-bular epithelial cells and subsequently reduced cisplatin-induced ferroptosis.In both HK-2 cells and primary renal tubular epithelial cells,Withaferin A upregulated NFE2L2 and FSP1 gene expression.The FSP1 gene was the most significantly upregulated gene.At the same time,it was found that the expression of FSP1 protein level was significantly upregulated by Withaferin A.After inter-fering with the expression of FSP1 in cells,Withaferin A alleviated the toxicity of cisplatin to HK-2 cells was significantly reduced.Conclusion:Withaferin A inhibited cisplatin-induced ferroptosis by upregulating FSP1 expression in renal proximal tubular epithe-lial cells,thereby alleviating cisplatin toxicity to the cells.关键词
FSP1/肾近端小管上皮细胞/醉茄素A/顺铂/铁死亡Key words
FSP1/Renal proximal tubular epithelial cells/Withaferin A/Cisplatin/Ferroptosis分类
中医学引用本文复制引用
钱睿,卢守燕,黄军悦,张鹏,马小梅,杨晓军,薛嵘..醉茄素A抑制肾近端小管上皮细胞铁死亡[J].海南医科大学学报,2025,31(9):667-674,8.基金项目
This study was supported by Research Project of Gansu Provincial People's Hospital(18GSSY5-22 and 23GSSYD-30) （18GSSY5-22 and 23GSSYD-30）
Natural Science Foundation of Gansu Province(22JR11RA256,21JR7RA639),and National Natural Science Foundation of China(81660398) 甘肃省人民医院院内科研项目(18GSSY5-22、23GSSYD-30) （22JR11RA256,21JR7RA639）
甘肃省自然科学基金项目(22JR11RA256 （）
21JR7RA639) （）
国家自然科学基金资助项目(81660398) （81660398）
