The multiomics landscape of serum exosomes during the development of sepsis.
The multiomics landscape of serum exosomes during the development of sepsis.
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脓毒症发展过程中血清外泌体的多组学全景。
DOI：
10.1016/j.jare.2021.11.005
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发表时间：
2022-07
影响因子：
10.7
通讯作者：
Jiang, Yong
中科院分区：
文献类型：
--
作者：
Li, Lei;Huang, Lin;Huang, Chenyang;Xu, Jia;Huang, Yukai;Luo, Haihua;Lu, Xinya;He, Shuyue;Yuan, Gang;Chen, Li;Han, Xue;Cao, Xusong;Jiang, Aolin;Liu, Cuiting;Shi, Junmin;Yang, Hong;Jiang, Yong
这项研究首次描述了败血症血清外切体的分子动力学特征。我们为脓毒症血清外切体中蛋白酶体介导的蛋白质降解提供了一个新的方向。脓毒症外切体介导的IL-10可能在减轻CLP小鼠AKI中起重要作用。脓毒症血清外切体通过调节维生素代谢参与脓毒症的调节。本研究提出的分子机制可能为脓毒症的治疗提供有益的启示。脓毒症是一种感染引起的严重炎症性疾病，导致多器官功能障碍。它仍然是一种高度致命的疾病，早期诊断和治疗效果不令人满意。包含败血症生物标志物和介体的循环外切体最近受到了关注，但进展远远不是最理想的。本研究旨在研究脓毒症患者血清外切体的分子动力学特征，并探讨其在脓毒症发病过程中可能的分子机制。应用高效液相色谱-串联质谱仪和RNA-SEQ技术检测了3例健康人和9例脓毒症患者不同时期血清外切体中外切体蛋白和RNA(包括mRNAs、lncRNAs和miRNAs)的动态变化。然后对盲肠结扎穿孔(CLP)模型小鼠进行整合基因组学分析，并通过qRT-PCR、LiquiChip分析和代谢组学分析对结果进行验证。共有354个蛋白质、195个mRNAs、82个lncRNAs和55个miRNAs被鉴定为败血症患者血清外切体的差异表达分子。综合组学分析表明，外切体组分与细胞因子风暴、补体和凝血级联反应、内皮屏障、20S蛋白酶体依赖的蛋白质降解和维生素代谢相关。重要的是，来自CLP小鼠的血清外切体预处理显著抑制了促炎症细胞因子的表达，并减轻了脓毒症小鼠的组织损伤。进一步的代谢组学分析表明，败血症血清外切体预处理显著影响CLP小鼠体内与维生素消化和吸收相关的代谢物。我们的研究首次描述了脓毒症发生发展过程中血清外切体的分子动力学格局，并通过整合的多组学分析提出了一些假想的分子机制，这可能为目前正在进行的抗败血症斗争提供有益的诊断和治疗见解。
The study for the first time describes the profile of molecular dynamics in septic serum exosomes. We provide a new direction into proteasome-mediated protein degradation in septic serum exosomes. IL-10 delivery by septic exosomes may play a vital role in alleviation of AKI of CLP mice. Septic serum exosomes participate in the modulation of sepsis by regulating vitamin metabolism. The molecular mechanisms proposed in the study may provide helpful insights for the therapy of sepsis. Sepsis is an infection-induced severe inflammatory disorder leading to multiple organ dysfunction. It remains a highly lethal condition for which early diagnosis and therapy achieve unsatisfactory results. Circulating exosomes containing biomarkers and mediators of sepsis have recently received attention, but the progress has been far from optimal. The present study focuses on the profiles of molecular dynamics in serum exosomes and explores the potential molecular mechanisms on serum exosomes during the process of sepsis. We used high-performance liquid chromatography-tandem mass spectrometry and RNA-seq to detect the dynamic profiles of exosome proteins and RNAs (including mRNAs, lncRNAs and miRNAs) in serum exosomes from 3 healthy individuals and 9 septic patients at the different stages. Then integrative multiomics analyses were performed and the results were validated by qRT-PCR, LiquiChip assay and metabolomics analysis on mice subjected to cecal ligation and puncture (CLP) modeling. A total of 354 proteins, 195 mRNAs, 82 lncRNAs and 55 miRNAs were identified as differentially expressed molecules in serum exosomes from septic patients. Integrative multiomics analysis showed that exosome components were associated with cytokine storm, complement and clotting cascades, the endothelial barrier, 20S proteasome-dependent protein degradation and vitamin metabolism. Importantly, pretreatment with serum exosomes derived from mice subjected to CLP significantly restrained proinflammatory cytokine expression and alleviated tissue injury in septic mice. Further metabolomics analysis demonstrated that pretreatment with septic serum exosomes significantly affected the metabolites associated with vitamin digestion and absorption in CLP mice. Our study for the first time describes the landscape of the molecular dynamics of serum exosomes during the development of sepsis and proposes some hypothetical molecular mechanisms by integrative multiomics analysis, which may provide helpful diagnostic and therapeutic insights for the ongoing battle against sepsis.
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影响因子：
120.7
作者：
Annane, Djillali;Cariou, Alain;Chevret, Sylvie
通讯作者：
Chevret, Sylvie
DOI：
10.1016/j.bbrc.2018.11.152
发表时间：
2019-01-08
影响因子：
3.1
作者：
Diakonov, Egor E.;Selenina, Anastasiia V.;Tsimokha, Anna S.
通讯作者：
Tsimokha, Anna S.
影响因子：
1.6
作者：
Doke, S;Inagaki, N;Tsuge, H
通讯作者：
Tsuge, H
影响因子：
16
作者：
Haraszti RA;Didiot MC;Sapp E;Leszyk J;Shaffer SA;Rockwell HE;Gao F;Narain NR;DiFiglia M;Kiebish MA;Aronin N;Khvorova A
通讯作者：
Khvorova A
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C