文献类型：期刊文献

英文题名：Based on bioinformatics, SESN2 negatively regulates ferroptosis induced by ischemia reperfusion via the System Xc-/GPX4 pathway

作者：Hu, Jiejie[1];Qin, Lijun[2];Zhu, Guoqiang[3];Ren, Jingjing[4];Wang, Hongxia[5];Jin, Jing[1];Zheng, Haixue[4];Li, Dan[4];Ge, Zhaoming[1]

第一作者：Hu, Jiejie

通信作者：Ge, ZM[1];Li, D[2]

机构：[1]Lanzhou Univ, Hosp 2, Dept Neurol, Lanzhou, Peoples R China;[2]Lanzhou Univ, Hosp 2, Dept Cardiol, Lanzhou, Peoples R China;[3]Lanzhou Jiaotong Univ, Sch Biol & Pharmaceut Engn, Lanzhou, Peoples R China;[4]Lanzhou Univ, Lanzhou Vet Res Inst, Chinese Acad Agr Sci,Coll Vet Med, Coll Vet Med,State Key Lab Vet Etiol Biol, Lanzhou, Peoples R China;[5]Gansu Univ Tradit Chinese Med, Dept Internal Med, Lanzhou, Peoples R China

第一机构：Lanzhou Univ, Hosp 2, Dept Neurol, Lanzhou, Peoples R China

通信机构：[1]corresponding author), Lanzhou Univ, Hosp 2, Dept Neurol, Lanzhou, Peoples R China;[2]corresponding author), Lanzhou Univ, Lanzhou Vet Res Inst, Chinese Acad Agr Sci,Coll Vet Med, Coll Vet Med,State Key Lab Vet Etiol Biol, Lanzhou, Peoples R China.

年份：2025

卷号：15

外文期刊名：FRONTIERS IN GENETICS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001418019600001)】；

基金：The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Natural Science Foundation of Gansu Province (24JRRA338), the Lanzhou University Second Hospital "CuiYing Technology Innovation" Program (CY2021-MS-B20), the Natural Science Foundation of Gansu Province (21JR11RA112), the Lanzhou Science and Technology Plan Project (2023-2-2), the Gansu Educational Technology Innovation Project (2022B-039), and the Gansu Science and Technology Plan Project (Innovation Base and Talent Plan) (20JR10FA663).

语种：英文

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

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.