微泡
败血症
外体
小RNA
促炎细胞因子
蛋白质组学
转录组
代谢组学
医学
生物
免疫学
炎症
生物信息学
生物化学
基因表达
基因
作者
Lei Li,Liwei Huang,Chenyang Huang,Jia Xu,Yung‐Cheng Huang,Haihua Luo,Xinya Lu,Shuyue He,Gang Yuan,Li Chen,Xue Han,Xusong Cao,Aolin Jiang,Cuiting Liu,Jun-Min Shi,Hong Yang,Yong Jiang
标识
DOI:10.1016/j.jare.2021.11.005
摘要
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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