E3连接酶TRIM21下调导致的OAS3去泛素化促进上皮细胞凋亡并驱动败血症诱发的急性肺损伤

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Biological Sciences Pub Date : 2024-10-14 eCollection Date: 2024-01-01 DOI:10.7150/ijbs.96089
Zhenfeng Chen, Bingqi Lin, Xiaodan Yao, Yihang Fang, Jinlian Liu, Ke Song, Lina Tuolihong, Zirui Zuo, Qi He, Xiaoxia Huang, Zhuanhua Liu, Qiaobing Huang, Qiulin Xu, Zhifeng Liu, Xiaohua Guo
{"title":"E3连接酶TRIM21下调导致的OAS3去泛素化促进上皮细胞凋亡并驱动败血症诱发的急性肺损伤","authors":"Zhenfeng Chen, Bingqi Lin, Xiaodan Yao, Yihang Fang, Jinlian Liu, Ke Song, Lina Tuolihong, Zirui Zuo, Qi He, Xiaoxia Huang, Zhuanhua Liu, Qiaobing Huang, Qiulin Xu, Zhifeng Liu, Xiaohua Guo","doi":"10.7150/ijbs.96089","DOIUrl":null,"url":null,"abstract":"<p><p>Patients with sepsis-induced acute lung injury (SALI) show a high mortality rate, and there is no effective treatment in the clinic for SALI but only symptomatic treatment as an option. Therefore, searching for effective targets is critical for the management of SALI. Ubiquitination is an essential post-translational protein modification involved in most pathophysiological processes. However, the relationship between ubiquitination and SALI remains largely unclear. In this study, we examined the ubiquitination modification changes in SALI, identified oligoadenylate synthetase 3 (OAS3) as a key candidate accounting for SALI from integrative multi-omics analysis and confirmed its role in promoting SALI and cell apoptosis in an animal model of cecal ligation and puncture-treated mice and a cellular model of LPS-treated MLE12 cells. Mechanistically, downregulation of E3 ligase TRIM21 mediates the reduction of OAS3 K48-linked polyubiquitination at the K1079 site in lung epithelial cells of a septic model, which leads to the increase of OAS3 protein level in a proteasomal-dependent manner. The upregulated OAS3 promotes epithelial cell apoptosis through its downstream effector molecule, RNase L. In summary, these findings unveil a previously unappreciated role of OAS3 ubiquitination in SALI and offer a promising perspective for further understanding the development of sepsis and potential therapeutic target for the treatment of SALI.</p>","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":null,"pages":null},"PeriodicalIF":8.2000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528449/pdf/","citationCount":"0","resultStr":"{\"title\":\"OAS3 Deubiquitination Due to E3 Ligase TRIM21 Downregulation Promotes Epithelial Cell Apoptosis and Drives Sepsis-induced Acute Lung Injury.\",\"authors\":\"Zhenfeng Chen, Bingqi Lin, Xiaodan Yao, Yihang Fang, Jinlian Liu, Ke Song, Lina Tuolihong, Zirui Zuo, Qi He, Xiaoxia Huang, Zhuanhua Liu, Qiaobing Huang, Qiulin Xu, Zhifeng Liu, Xiaohua Guo\",\"doi\":\"10.7150/ijbs.96089\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Patients with sepsis-induced acute lung injury (SALI) show a high mortality rate, and there is no effective treatment in the clinic for SALI but only symptomatic treatment as an option. Therefore, searching for effective targets is critical for the management of SALI. Ubiquitination is an essential post-translational protein modification involved in most pathophysiological processes. However, the relationship between ubiquitination and SALI remains largely unclear. In this study, we examined the ubiquitination modification changes in SALI, identified oligoadenylate synthetase 3 (OAS3) as a key candidate accounting for SALI from integrative multi-omics analysis and confirmed its role in promoting SALI and cell apoptosis in an animal model of cecal ligation and puncture-treated mice and a cellular model of LPS-treated MLE12 cells. Mechanistically, downregulation of E3 ligase TRIM21 mediates the reduction of OAS3 K48-linked polyubiquitination at the K1079 site in lung epithelial cells of a septic model, which leads to the increase of OAS3 protein level in a proteasomal-dependent manner. The upregulated OAS3 promotes epithelial cell apoptosis through its downstream effector molecule, RNase L. In summary, these findings unveil a previously unappreciated role of OAS3 ubiquitination in SALI and offer a promising perspective for further understanding the development of sepsis and potential therapeutic target for the treatment of SALI.</p>\",\"PeriodicalId\":13762,\"journal\":{\"name\":\"International Journal of Biological Sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":8.2000,\"publicationDate\":\"2024-10-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11528449/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Biological Sciences\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.7150/ijbs.96089\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Biological Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.7150/ijbs.96089","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

脓毒症诱发的急性肺损伤(SALI)患者死亡率很高,目前临床上还没有有效治疗 SALI 的方法,只能选择对症治疗。因此,寻找有效的靶点对于治疗 SALI 至关重要。泛素化是一种重要的蛋白质翻译后修饰,参与了大多数病理生理过程。然而,泛素化与 SALI 之间的关系在很大程度上仍不清楚。在本研究中,我们研究了 SALI 中泛素化修饰的变化,通过多组学整合分析确定了寡腺苷酸合成酶 3(OAS3)作为 SALI 的关键候选蛋白,并在盲肠结扎和穿刺处理的小鼠动物模型和 LPS 处理的 MLE12 细胞模型中证实了其在促进 SALI 和细胞凋亡中的作用。从机理上讲,E3连接酶TRIM21的下调介导了败血症模型肺上皮细胞中OAS3 K48连接的多泛素化在K1079位点的减少,从而导致OAS3蛋白水平以蛋白酶体依赖的方式升高。总之,这些发现揭示了 OAS3 泛素化在 SALI 中以前未被认识到的作用,为进一步了解脓毒症的发展和治疗 SALI 的潜在治疗靶点提供了一个前景广阔的视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
OAS3 Deubiquitination Due to E3 Ligase TRIM21 Downregulation Promotes Epithelial Cell Apoptosis and Drives Sepsis-induced Acute Lung Injury.

Patients with sepsis-induced acute lung injury (SALI) show a high mortality rate, and there is no effective treatment in the clinic for SALI but only symptomatic treatment as an option. Therefore, searching for effective targets is critical for the management of SALI. Ubiquitination is an essential post-translational protein modification involved in most pathophysiological processes. However, the relationship between ubiquitination and SALI remains largely unclear. In this study, we examined the ubiquitination modification changes in SALI, identified oligoadenylate synthetase 3 (OAS3) as a key candidate accounting for SALI from integrative multi-omics analysis and confirmed its role in promoting SALI and cell apoptosis in an animal model of cecal ligation and puncture-treated mice and a cellular model of LPS-treated MLE12 cells. Mechanistically, downregulation of E3 ligase TRIM21 mediates the reduction of OAS3 K48-linked polyubiquitination at the K1079 site in lung epithelial cells of a septic model, which leads to the increase of OAS3 protein level in a proteasomal-dependent manner. The upregulated OAS3 promotes epithelial cell apoptosis through its downstream effector molecule, RNase L. In summary, these findings unveil a previously unappreciated role of OAS3 ubiquitination in SALI and offer a promising perspective for further understanding the development of sepsis and potential therapeutic target for the treatment of SALI.

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
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
期刊最新文献
Targeting mitochondria by lipid-selenium conjugate drug results in malate/fumarate exhaustion and induces mitophagy-mediated necroptosis suppression. Mechanistic study of celastrol-mediated inhibition of proinflammatory activation of macrophages in IgA nephropathy via down-regulating ECM1. Micro(nano)plastics: an Emerging Burden for Human Health. New insights into non-small cell lung cancer bone metastasis: mechanisms and therapies. SUMOylation modification of HNRNPK at the K422 site promotes invasion in glioblastoma.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1