Perilipin-2 mediates ferroptosis in oligodendrocyte progenitor cells and myelin injury after ischemic stroke  

作　　者：Jian Yang Jiang Wu Xueshun Xie Pengfei Xia Jinxin Lu Jiale Liu Lei Bai Xiang Li Zhengquan Yu Haiying Li 

机构地区：[1]Department of Neurosurgery&Brain and Nerve Research Laboratory,The First Affiliated Hospital of Soochow University,Suzhou,Jiangsu Province,China [2]Institute of Stroke Research,Soochow University,Suzhou,Jiangsu Province,China

出　　处：《Neural Regeneration Research》2025年第7期2015-2028,共14页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,Nos.82071307(to HL),82271362(to HL),82171294(to JW),82371303(to JW),and 82301460(to PX);the Natural Science Foundation of Jiangsu Province,No.BK20211552(to HL);Suzhou Medical Technology Innovation Project-Clinical Frontier,No.SKY2022002(to ZY);the Science and Education Foundation for Health of Suzhou for Youth,No.KJXW2023001(to XL)。

摘　　要：Differentiation of oligodendrocyte progenitor cells into mature myelin-forming oligodendrocytes contributes to remyelination.Failure of remyelination due to oligodendrocyte progenitor cell death can result in severe nerve damage.Ferroptosis is an iron-dependent form of regulated cell death caused by membrane rupture induced by lipid peroxidation,and plays an important role in the pathological process of ischemic stroke.However,there are few studies on oligodendrocyte progenitor cell ferroptosis.We analyzed transcriptome sequencing data from GEO databases and identified a role of ferroptosis in oligodendrocyte progenitor cell death and myelin injury after cerebral ischemia.Bioinformatics analysis suggested that perilipin-2(PLIN2)was involved in oligodendrocyte progenitor cell ferroptosis.PLIN2 is a lipid storage protein and a marker of hypoxia-sensitive lipid droplet accumulation.For further investigation,we established a mouse model of cerebral ischemia/reperfusion.We found significant myelin damage after cerebral ischemia,as well as oligodendrocyte progenitor cell death and increased lipid peroxidation levels around the infarct area.The ferroptosis inhibitor,ferrostatin-1,rescued oligodendrocyte progenitor cell death and subsequent myelin injury.We also found increased PLIN2 levels in the peri-infarct area that co-localized with oligodendrocyte progenitor cells.Plin2 knockdown rescued demyelination and improved neurological deficits.Our findings suggest that targeting PLIN2 to regulate oligodendrocyte progenitor cell ferroptosis may be a potential therapeutic strategy for rescuing myelin damage after cerebral ischemia.

关 键 词：BIOINFORMATICS bulk RNA sequencing ferroptosis ischemic stroke myelin injury oligodendrocyte progenitor cell perilipin-2 single-cell RNA sequencing 

分 类 号：R743.3[医药卫生—神经病学与精神病学]