Ying Wang, Ting Wang, Qian Xiang, Na Li, Jun Wang, Jiahao Liu, Yan Zhang, Tao Yang, Jinjun Bian
{"title":"GPR116通过抑制系统Xc-/GSH/GPX4促进脓毒症诱导的肝损伤中的铁凋亡。","authors":"Ying Wang, Ting Wang, Qian Xiang, Na Li, Jun Wang, Jiahao Liu, Yan Zhang, Tao Yang, Jinjun Bian","doi":"10.1007/s10565-023-09815-8","DOIUrl":null,"url":null,"abstract":"<p><p>The disease sepsis is caused by an infection that damages organs. Liver injury, with ferroptosis playing a key role, is an early sign of sepsis. G protein-coupled receptor 116 (GPR116) is essential in the maintenance of functional homeostasis in various systems of the body and has been proven to play a protective role in septic lung injury. However, it's role in septic liver injury remains unclear. In this study, we found that hepatic ferroptosis during sepsis was accompanied by GPR116 upregulation. Hepatocyte-specific GPR116 gene deletion can prevent hepatic ferroptosis, thereby alleviating sepsis-induced liver dysfunction and improving mouse survival, which was verified in vivo. Mechanistically, GPR116 aggravated mitochondrial damage and lipid peroxidation in hepatocytes by inhibiting system Xc<sup>-</sup>/GSH/GPX4 in overexpression experiments. In conclusion, we have identified GPR116 as a vital mediator of ferroptosis in sepsis-induced liver injury. It is thus an attractive therapeutic target in sepsis.</p>","PeriodicalId":9672,"journal":{"name":"Cell Biology and Toxicology","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"GPR116 promotes ferroptosis in sepsis-induced liver injury by suppressing system Xc<sup>-</sup>/GSH/GPX4.\",\"authors\":\"Ying Wang, Ting Wang, Qian Xiang, Na Li, Jun Wang, Jiahao Liu, Yan Zhang, Tao Yang, Jinjun Bian\",\"doi\":\"10.1007/s10565-023-09815-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The disease sepsis is caused by an infection that damages organs. Liver injury, with ferroptosis playing a key role, is an early sign of sepsis. G protein-coupled receptor 116 (GPR116) is essential in the maintenance of functional homeostasis in various systems of the body and has been proven to play a protective role in septic lung injury. However, it's role in septic liver injury remains unclear. In this study, we found that hepatic ferroptosis during sepsis was accompanied by GPR116 upregulation. Hepatocyte-specific GPR116 gene deletion can prevent hepatic ferroptosis, thereby alleviating sepsis-induced liver dysfunction and improving mouse survival, which was verified in vivo. Mechanistically, GPR116 aggravated mitochondrial damage and lipid peroxidation in hepatocytes by inhibiting system Xc<sup>-</sup>/GSH/GPX4 in overexpression experiments. In conclusion, we have identified GPR116 as a vital mediator of ferroptosis in sepsis-induced liver injury. It is thus an attractive therapeutic target in sepsis.</p>\",\"PeriodicalId\":9672,\"journal\":{\"name\":\"Cell Biology and Toxicology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2023-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Biology and Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10565-023-09815-8\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/6/2 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biology and Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10565-023-09815-8","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/6/2 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
GPR116 promotes ferroptosis in sepsis-induced liver injury by suppressing system Xc-/GSH/GPX4.
The disease sepsis is caused by an infection that damages organs. Liver injury, with ferroptosis playing a key role, is an early sign of sepsis. G protein-coupled receptor 116 (GPR116) is essential in the maintenance of functional homeostasis in various systems of the body and has been proven to play a protective role in septic lung injury. However, it's role in septic liver injury remains unclear. In this study, we found that hepatic ferroptosis during sepsis was accompanied by GPR116 upregulation. Hepatocyte-specific GPR116 gene deletion can prevent hepatic ferroptosis, thereby alleviating sepsis-induced liver dysfunction and improving mouse survival, which was verified in vivo. Mechanistically, GPR116 aggravated mitochondrial damage and lipid peroxidation in hepatocytes by inhibiting system Xc-/GSH/GPX4 in overexpression experiments. In conclusion, we have identified GPR116 as a vital mediator of ferroptosis in sepsis-induced liver injury. It is thus an attractive therapeutic target in sepsis.
期刊介绍:
Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.