数字农科院2.0

Based on bioinformatics, SESN2 negatively regulates ferroptosis induced by ischemia reperfusion via the System Xc−/GPX4 pathway

文献类型： 外文期刊

作者： Jiejie Hu;Lijun Qin;Guoqiang Zhu;Jingjing Ren;Hongxia Wang;Jing Jin;Haixue Zheng;Dan Li;Zhaoming Ge

作者机构：

关键词： brain microvascular endothelial cells;ferroptosis;hub gene;ischemia/reperfusion;RNA-seq;SESN2;system Xc-

期刊名称： Frontiers in Genetics

ISSN： 1664-8021

年卷期： 2025 年 15 卷

页码：

收录情况： SCIE（2025版）

摘要： Introduction: Cerebral ischemia–reperfusion (IR) causes severe secondary brain injury. Previous studies have demonstrated that ferroptosis is involved in IR-induced brain injury. However, whether IR induces ferroptosis in brain microvascular endothelial cells (BMVECs) is not fully understood. Materials and methods: Oxygen–glucose deprivation/reoxygenation (OGDR) was performed in bEND.3 cells to mimic IR injury in vitro, and a focal cerebral IR model was created in C57BL/6 mice. Transcriptomic sequencing of the cells was performed first, followed by bioinformatics analysis. Differentially expressed gene (DEG) enrichment analysis highlighted ferroptosis-related pathways. Results: Using Venn analysis, nine ferroptosis-related DEGs were identified, namely, Slc3a2, Slc7a11, Ccn2, Tfrc, Atf3, Chac1, Gch1, Lcn2, and Sesn2. Protein–protein interaction (PPI) analysis combined with molecular complex detection (MCODE) identified six hub genes, namely, Ddit3, Atf3, Sesn2, Trib3, Ppp1r15a, and Gadd45a. Spearman’s correlation analysis revealed a significant correlation between the hub genes and ferroptosis-related DEGs. After reperfusion, the levels of ferroptosis indicators were elevated, and the expression of the ferroptosis-related proteins Xc− and GPX4 decreased. SESN2 is a hub gene and key antioxidant regulator. SESN2 silencing reduced the expression of System Xc− and GPX4, whereas overexpression of SESN2 promoted the expression of System Xc− and GPX4. Discussion: These results suggest that SESN2 is a negative regulator of ferroptosis. Enhancing the expression of SESN2 can alleviate ferroptosis through the activation of the System Xc−/GPX4 pathway. By integrating bioinformatics analysis with mechanistic exploration, this study revealed that ferroptosis plays a crucial role in IR-induced BMVECs injury, with SESN2 acting as a negative regulator via the System Xc−/GPX4 pathway.

分类号：

  • 相关文献

[1]WGCNA revealed a comprehensive gene co-expression network associated with brown spot in Nicotiana tabacum L.. Zhan Shen,Zipeng Jiang,Yalin Bai,Yangyang Li,Chan Qiao,Caihong Jiang,Lirui Cheng,Yuanying Wang,Yinchao Zhang,Aiguo Yang,Dan Liu. 2025

[2]Transcriptome-hormone network analysis tentatively reveals a chalcone synthase 1-dependent pathway for tobacco mosaic virus resistance in tobacco. Fuxin Li,Min Ren,Lihua Li,Jiang Wu,Fengjie Wei,Xiaoling Qu,Ying Tong,Xiuming Wu,Yangyang Sun,Aiguo Yang,Shuai Chen,Yinchao Zhang. 2025

[3]Linkage and association analyses reveal that hub genes in energy-flow and lipid biosynthesis pathways form a cluster in upland cotton. Gong J.,Peng Y.,Yu J.,Pei W.,Zhang Z.,Fan D.,Liu L.,Xiao X.,Liu R.,Lu Q.,Li P.,Shang H.,Shi Y.,Li J.,Ge Q.,Liu A.,Deng X.,Fan S.,Pan J.,Chen Q.,Yuan Y.,Gong W.. 2022

[4]RNA sequencing identifies key genes involved in intramuscular fat deposition in chickens at different developmental stages. Jinmei Zhu,Yongli Wang,Yongchun Su,Maiqing Zheng,Huanxian Cui,Zhiwu Chen. 2024

[5]Integrated Analysis of the Metabolome and Transcriptome During Apple Ripening to Highlight Aroma Determinants in Ningqiu Apples. Jun Ma,Guangzong Li,Yannan Chu,Haiying Yue,Zehua Xu,Jiaqi Wu,Xiaolong Li,Yonghua Jia. 2025

[6]河流型水牛TGF-β基因家族鉴定及其胚胎发育早期的表达分析. 庞春英,梁莎莎,马小娅,陆杏蓉,段安琴,邓廷贤,黄韵琪,梁贤威. 2020

[7]拟南芥ago1-27突变体的RNA-seq分析. 马轩,李盛本,莫蓓莘,曹晓风,陈雪梅. 2017

[8]本生烟响应蛋白激发子PevD1的差异表达基因鉴定与分析. 梁颖博,李泽,邱德文,曾洪梅,李广悦,杨秀芬. 2019

[9]基于RNA-Seq的甘蔗主茎和分蘖茎转录组建立及初步分析. 丘立杭,罗含敏,陈荣发,黄杏,陈忠良,范业赓,陈栋,李杨瑞,吴建明. 2018

[10]基于RNA-Seq技术的o2胚乳差异表达分析. 朱慧,周志强,张东民,周昱婕,张晓星,刘红军,宋丽雅,李明顺. 2019

[11]雏鸡红细胞免疫相关基因差异表达的时序性研究. 贾悦,李月健,喻进,张晨亮,李娜娜,卢晓晓,张宁,李欣,张鼎,郝卫芳,马海利,高文伟,赵宇军,高诗敏,李建慧,李桂兰,闫芳,韩凌霞,宁官保,田文霞. 2015

[12]志贺菌耐药性与非编码RNA的关系研究. 刘翠翠,魏小娟,周绪正,李冰,牛建荣,王婧,朱阵,张继瑜. 2014

[13]应用RNA-seq数据开展鸭基因组可变剪接的鉴定与分析. 徐铁山,顾丽红,侯水生,叶保国. 2016

[14]基于RNA-Seq的稻瘟病菌Δznf1突变体的表达谱分析. 岳晓凤,阙亚伟,王政逸. 2016

[15]基于RNA-seq技术开发中间偃麦草基因组特异分子标记. 崔雨,鲍印广,王洪刚,李兴锋. 2016

[16]基因本体论在福氏志贺菌转录组研究中的应用. 朱阵,刘翠翠,王婧,张继瑜,魏小娟,周绪正,李冰,郭肖. 2014

[17]基于RNA-seq的能源植物芒转录组分析. 张贤,王建红,喻曼,曹凯,庄俐,徐昌旭,曹卫东. 2015

[18]利用RNA-Seq技术筛选不同海拔地区山羊转录组SNP. 姚娜,张文广,张兵,赵倩君,左清清,董坤哲,冯爱琴,马月辉. 2012

[19]棉花纤维发育早期RNA-Seq转录组分析. 李锡花,吴嫚,于霁雯,张金发,范术丽,宋美珍,庞朝友,喻树迅. 2013

[20]转录组测序技术的研究和应用进展. 崔凯,吴伟伟,刁其玉. 2019

作者其他论文 更多>>