MYOCD和SRF介导的MLCK转录可防止多形核中性粒细胞在脓毒症相关急性肺损伤中发生铁变态反应。

IF 3.3 4区 医学 Q3 IMMUNOLOGY
Immunologic Research Pub Date : 2024-12-01 Epub Date: 2024-08-28 DOI:10.1007/s12026-024-09529-x
Danfeng Pan, Qiu Wu, Chunfeng Zhang, Tao Qin, Tian Jiang, Ximei Wu, Fugen Wu
{"title":"MYOCD和SRF介导的MLCK转录可防止多形核中性粒细胞在脓毒症相关急性肺损伤中发生铁变态反应。","authors":"Danfeng Pan, Qiu Wu, Chunfeng Zhang, Tao Qin, Tian Jiang, Ximei Wu, Fugen Wu","doi":"10.1007/s12026-024-09529-x","DOIUrl":null,"url":null,"abstract":"<p><p>Persistent activation of polymorphonuclear neutrophils (PMNs) plays a crucial role in the development of sepsis-related acute lung injury (ALI). This study investigated key molecular mechanisms involved in the hyperactivation of PMNs during ALI. A mouse model of sepsis-related ALI was generated by lipopolysaccharide (LPS) injection. RNA sequencing identified myosin light chain kinase (MLCK) as the most significant differentially expressed gene (DEG) between PMNs isolated from model and control mice. Myocardin (MYOCD) and serum response factor (SRF) were two of the DEGs that could promote transcription of MLCK by binding to its promoter. Either knockdown of MLCK, MYOCD, or SRF ameliorated dysfunction and edema in the lungs of LPS-treated mice. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that the DEGs are enriched in a ferroptosis-related signaling pathway. The MLCK, MYOCD, or SRF knockdown increased contents of ROS, MDA, ferritin, and ferrous iron, and reduced levels of GSH and GPX4 in the PMNs. However, the MLCK overexpression restored ferroptosis resistance and activity of the PMNs, resulting in increased lung injury. Collectively, this study demonstrates that MYOCD and SRF-mediated MLCK upregulation is correlated with ferroptosis resistance and hyperactivation of PMNs in sepsis-related ALI.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":" ","pages":"1299-1312"},"PeriodicalIF":3.3000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"MYOCD and SRF-mediated MLCK transcription prevents polymorphonuclear neutrophils from ferroptosis in sepsis-related acute lung injury.\",\"authors\":\"Danfeng Pan, Qiu Wu, Chunfeng Zhang, Tao Qin, Tian Jiang, Ximei Wu, Fugen Wu\",\"doi\":\"10.1007/s12026-024-09529-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Persistent activation of polymorphonuclear neutrophils (PMNs) plays a crucial role in the development of sepsis-related acute lung injury (ALI). This study investigated key molecular mechanisms involved in the hyperactivation of PMNs during ALI. A mouse model of sepsis-related ALI was generated by lipopolysaccharide (LPS) injection. RNA sequencing identified myosin light chain kinase (MLCK) as the most significant differentially expressed gene (DEG) between PMNs isolated from model and control mice. Myocardin (MYOCD) and serum response factor (SRF) were two of the DEGs that could promote transcription of MLCK by binding to its promoter. Either knockdown of MLCK, MYOCD, or SRF ameliorated dysfunction and edema in the lungs of LPS-treated mice. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that the DEGs are enriched in a ferroptosis-related signaling pathway. The MLCK, MYOCD, or SRF knockdown increased contents of ROS, MDA, ferritin, and ferrous iron, and reduced levels of GSH and GPX4 in the PMNs. However, the MLCK overexpression restored ferroptosis resistance and activity of the PMNs, resulting in increased lung injury. Collectively, this study demonstrates that MYOCD and SRF-mediated MLCK upregulation is correlated with ferroptosis resistance and hyperactivation of PMNs in sepsis-related ALI.</p>\",\"PeriodicalId\":13389,\"journal\":{\"name\":\"Immunologic Research\",\"volume\":\" \",\"pages\":\"1299-1312\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Immunologic Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12026-024-09529-x\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/28 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunologic Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12026-024-09529-x","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/28 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

多形核中性粒细胞(PMNs)的持续活化在脓毒症相关急性肺损伤(ALI)的发展过程中起着至关重要的作用。本研究探讨了 ALI 期间多形核中性粒细胞过度活化的关键分子机制。通过注射脂多糖(LPS)建立了脓毒症相关 ALI 的小鼠模型。通过 RNA 测序发现,肌球蛋白轻链激酶(MLCK)是分离自模型小鼠和对照小鼠的 PMNs 之间最显著的差异表达基因(DEG)。肌球蛋白(MYOCD)和血清反应因子(SRF)是其中两个可通过与其启动子结合促进MLCK转录的DEG。无论是敲除MLCK、MYOCD还是SRF,都能改善LPS处理小鼠肺部的功能障碍和水肿。京都基因和基因组百科全书》富集分析表明,DEGs富集于铁变态反应相关的信号通路中。MLCK、MYOCD或SRF敲除会增加PMN中ROS、MDA、铁蛋白和亚铁的含量,并降低GSH和GPX4的水平。然而,MLCK的过表达恢复了PMNs的铁变态反应抵抗力和活性,导致肺损伤加重。总之,这项研究表明,MYOCD 和 SRF 介导的 MLCK 上调与脓毒症相关 ALI 中 PMNs 的抗铁蛋白沉积和过度激活有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

MYOCD and SRF-mediated MLCK transcription prevents polymorphonuclear neutrophils from ferroptosis in sepsis-related acute lung injury.

MYOCD and SRF-mediated MLCK transcription prevents polymorphonuclear neutrophils from ferroptosis in sepsis-related acute lung injury.

Persistent activation of polymorphonuclear neutrophils (PMNs) plays a crucial role in the development of sepsis-related acute lung injury (ALI). This study investigated key molecular mechanisms involved in the hyperactivation of PMNs during ALI. A mouse model of sepsis-related ALI was generated by lipopolysaccharide (LPS) injection. RNA sequencing identified myosin light chain kinase (MLCK) as the most significant differentially expressed gene (DEG) between PMNs isolated from model and control mice. Myocardin (MYOCD) and serum response factor (SRF) were two of the DEGs that could promote transcription of MLCK by binding to its promoter. Either knockdown of MLCK, MYOCD, or SRF ameliorated dysfunction and edema in the lungs of LPS-treated mice. Kyoto Encyclopedia of Genes and Genomes enrichment analysis suggested that the DEGs are enriched in a ferroptosis-related signaling pathway. The MLCK, MYOCD, or SRF knockdown increased contents of ROS, MDA, ferritin, and ferrous iron, and reduced levels of GSH and GPX4 in the PMNs. However, the MLCK overexpression restored ferroptosis resistance and activity of the PMNs, resulting in increased lung injury. Collectively, this study demonstrates that MYOCD and SRF-mediated MLCK upregulation is correlated with ferroptosis resistance and hyperactivation of PMNs in sepsis-related ALI.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Immunologic Research
Immunologic Research 医学-免疫学
CiteScore
6.90
自引率
0.00%
发文量
83
审稿时长
6-12 weeks
期刊介绍: IMMUNOLOGIC RESEARCH represents a unique medium for the presentation, interpretation, and clarification of complex scientific data. Information is presented in the form of interpretive synthesis reviews, original research articles, symposia, editorials, and theoretical essays. The scope of coverage extends to cellular immunology, immunogenetics, molecular and structural immunology, immunoregulation and autoimmunity, immunopathology, tumor immunology, host defense and microbial immunity, including viral immunology, immunohematology, mucosal immunity, complement, transplantation immunology, clinical immunology, neuroimmunology, immunoendocrinology, immunotoxicology, translational immunology, and history of immunology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信