{"title":"msc - ev通过抑制net对内皮细胞粘附连接的损伤,减轻败血症诱导的急性肺损伤","authors":"Yuwen Shao , Dan Wu , Changhong Miao , Hao Zhang","doi":"10.1016/j.molimm.2025.07.004","DOIUrl":null,"url":null,"abstract":"<div><div>Neutrophil extracellular traps (NETs) play a crucial role in the progression of sepsis-induced acute lung injury (SI-ALI). Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) are considered to have potential therapeutic effects on SI-ALI. Nevertheless, a comprehensive understanding of the precise mechanism is currently lacking. This study intends to illustrate the therapeutic mechanisms of MSC-EVs against NET-mediated SI-ALI. In vivo and in vitro experiments demonstrate that NETs reduced the expression of VE-cadherin through calpain 1/2 activation, thereby impairing endothelial barrier function and exacerbating the pathogenesis of SI-ALI. MSC-EVs were found to alleviate SI-ALI by reducing the formation of NETs. Additionally, MSC-EVs inhibited NET generation by shifting NETosis to apoptosis through the ROS/AKT pathway. This study delineates the pathogenic role of NET-induced endothelial injury in SI-ALI and promotes MSC-EVs as a novel therapeutic approach for this disease.</div></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"185 ","pages":"Pages 6-17"},"PeriodicalIF":3.0000,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"MSC-EVs alleviate sepsis-induced acute lung injury through inhibiting NET-triggered damage to adherens junctions of endothelial cells\",\"authors\":\"Yuwen Shao , Dan Wu , Changhong Miao , Hao Zhang\",\"doi\":\"10.1016/j.molimm.2025.07.004\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Neutrophil extracellular traps (NETs) play a crucial role in the progression of sepsis-induced acute lung injury (SI-ALI). Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) are considered to have potential therapeutic effects on SI-ALI. Nevertheless, a comprehensive understanding of the precise mechanism is currently lacking. This study intends to illustrate the therapeutic mechanisms of MSC-EVs against NET-mediated SI-ALI. In vivo and in vitro experiments demonstrate that NETs reduced the expression of VE-cadherin through calpain 1/2 activation, thereby impairing endothelial barrier function and exacerbating the pathogenesis of SI-ALI. MSC-EVs were found to alleviate SI-ALI by reducing the formation of NETs. Additionally, MSC-EVs inhibited NET generation by shifting NETosis to apoptosis through the ROS/AKT pathway. This study delineates the pathogenic role of NET-induced endothelial injury in SI-ALI and promotes MSC-EVs as a novel therapeutic approach for this disease.</div></div>\",\"PeriodicalId\":18938,\"journal\":{\"name\":\"Molecular immunology\",\"volume\":\"185 \",\"pages\":\"Pages 6-17\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-07-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S016158902500166X\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S016158902500166X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
MSC-EVs alleviate sepsis-induced acute lung injury through inhibiting NET-triggered damage to adherens junctions of endothelial cells
Neutrophil extracellular traps (NETs) play a crucial role in the progression of sepsis-induced acute lung injury (SI-ALI). Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) are considered to have potential therapeutic effects on SI-ALI. Nevertheless, a comprehensive understanding of the precise mechanism is currently lacking. This study intends to illustrate the therapeutic mechanisms of MSC-EVs against NET-mediated SI-ALI. In vivo and in vitro experiments demonstrate that NETs reduced the expression of VE-cadherin through calpain 1/2 activation, thereby impairing endothelial barrier function and exacerbating the pathogenesis of SI-ALI. MSC-EVs were found to alleviate SI-ALI by reducing the formation of NETs. Additionally, MSC-EVs inhibited NET generation by shifting NETosis to apoptosis through the ROS/AKT pathway. This study delineates the pathogenic role of NET-induced endothelial injury in SI-ALI and promotes MSC-EVs as a novel therapeutic approach for this disease.
期刊介绍:
Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to:
Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology
Mechanisms of induction, regulation and termination of innate and adaptive immunity
Intercellular communication, cooperation and regulation
Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc)
Mechanisms of action of the cells and molecules of the immune system
Structural analysis
Development of the immune system
Comparative immunology and evolution of the immune system
"Omics" studies and bioinformatics
Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc)
Technical developments.