Proteomic Profiling of LPS-Induced Macrophage-Derived Exosomes Indicates Their Involvement in Acute Liver Injury
Proteomic Profiling of LPS-Induced Macrophage-Derived Exosomes Indicates Their Involvement in Acute Liver Injury
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LPS 诱导的巨噬细胞衍生的外泌体的蛋白质组学分析表明它们参与急性肝损伤
DOI：
10.1002/pmic.201800274
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发表时间：
2019-02-01
期刊：
影响因子：
3.4
通讯作者：
Li, Xu
中科院分区：
文献类型：
--
作者：
Wang, Guozhen;Jin, Siyi;Li, Xu
胞外体通常参与细胞通讯和信号传递。巨噬细胞在脂多糖(LPS)诱导的脓毒症中起关键作用。然而，内毒素诱导的巨噬细胞来源的外切体的分子比较还没有得到很好的分析。巨噬细胞-外切体被确认，并用相对和绝对定量(ITRAQ)质谱仪的等量标签研究这些外切体的蛋白质组成。巨噬细胞-外切体中共鉴定出5056种蛋白质。我们发现，与对照外切体相比，内毒素处理的巨噬细胞外切体中有341个蛋白质增加，363个蛋白质减少。此外，基因本体论分析表明，巨噬细胞-外切体蛋白主要与细胞、细胞器、胞外区和膜相连。生物信息学分析还表明，这些蛋白质主要参与细胞过程、单个生物过程、代谢过程和生物调节。京都百科全书的基因和基因组分析显示，在这341个上调的蛋白质中，有22个蛋白质参与了NOD样受体信号通路。最后，肝细胞可以摄取巨噬细胞-外切体，从而在体外和体内激活NLRP3炎症体。这些数据强调了巨噬细胞-外切体在脓毒症所致肝损伤中的基本重要性。因此，iTRAQ蛋白质组学策略为巨噬细胞来源的外切体带来了新的见解。这可能会提高我们对巨噬细胞-外切体的功能以及它们作为脓毒症治疗靶点的可能用途的理解。
Exosomes are typically involved in cellular communication and signaling. Macrophages play a key role in lipopolysaccharide (LPS)-induced sepsis. However, the molecular comparison of exosomes derived from LPS-induced macrophage has not been well analyzed. The macrophage-exosomes are validated and the protein composition of those exosomes are investigated by isobaric tags for relative and absolute quantification (iTRAQ) mass spectrometry. A total of 5056 proteins are identified in macrophage-exosomes. We discovered 341 increased proteins and 363 reduced proteins in LPS-treated macrophage-exosomes compared with control exosomes. In addition, gene ontology analysis demonstrates that macrophage-exosomes proteins are mostly linked to cell, organelle, extracellular region, and membrane. The bioinformatics analysis also indicates that these proteins are mainly involved in cellular process, single-organism process, metabolic process, and biological regulation. Among these 341 upregulated proteins, Kyoto Encyclopedia of Genes and Genomes analysis reveals that 22 proteins are involved in the NOD-like receptor signaling pathway. Finally, hepatocytes can uptake macrophage-exosomes and subsequently NLRP3 inflammasome is activated in vitro and in vivo. These data emphasize the fundamental importance of macrophage-exosomes in sepsis-induced liver injury. Therefore, the iTRAQ proteomic strategy brings new insights into macrophage-derived exosomes. It may improve our understanding of macrophage-exosomes' functions and their possible use as therapeutic targets for sepsis.