miRNAomics analysis reveals the promoting effects of cigarette smoke extract-treated Beas-2B-derived exosomes on macrophage polarization
miRNAomics analysis reveals the promoting effects of cigarette smoke extract-treated Beas-2B-derived exosomes on macrophage polarization
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DOI：
10.1016/j.bbrc.2021.07.093
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发表时间：
2021-08-05
影响因子：
3.1
通讯作者：
Li, Peibo
中科院分区：
文献类型：
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作者：
Chen, Zhen;Wu, Hao;Li, Peibo
吸入香烟烟雾会导致呼吸道和实质炎症，使吸烟者容易患上多种肺部疾病，如慢性阻塞性肺病。巨噬细胞极化是炎症的一个重要特征，参与了肺部炎症的发展。Exosome及其负载的miRNAs为肺泡巨噬细胞和肺上皮细胞之间的串扰提供了一种媒介，以维持肺内环境的稳定。在这项研究中，我们用CSE处理BEAS-2B，以推测Beas2B衍生的外体对巨噬细胞极化的影响，并进行外体miRNA组学分析，以探讨其机制。我们发现CSE处理的BEAS-2B来源的外切体不仅能增加CD86(+)、CD80(+)、CD163(+)和CD206刺细胞的百分率，而且能诱导巨噬细胞分泌TNF-α、IL-6、iNOS、IL-10、Arg-1和TGF-β，表明RAW264.7巨噬细胞的M1和M2极化均有促进作用。我们进行了miRNA组学分析，鉴定了27个差异表达的外体miRNAs，如miR-29a-3p和miR-1307-5p。接下来，通过TargetScan和Miranda的预测，我们获得了这些miRNAs的14942个靶基因，如SCN1A和PLEKHA1。我们利用KEGG富集法对这些靶点进行分析，以确定可能的途径，如PI3K-Akt信号通路和MAPK信号通路对巨噬细胞极化的调节。我们进一步发现miR-21-3p或miR-27b-3p可能在通过miRNA干扰促进CSE-Exo对巨噬细胞极化的促进中起关键作用。总之，这项研究为香烟烟雾相关肺部疾病的诊断和治疗策略提供了新的信息。(C)2021 Elsevier Inc.保留所有权利。
Inhalation of cigarette smoke induces airway and parenchyma inflammation that predisposes smokers to multiple lung diseases such as COPD. Macrophage polarization, an important specifying feature of inflammation, is involved in the progression of pulmonary inflammation. Exosomes and their loaded miRNAs provide a medium for cross-talk between alveolar macrophages and lung epithelial cells to maintain lung homeostasis. In this study, we treated Beas-2B with CSE to speculate the effects of Beas2B-derived exosomes on macrophage polarization and performed exosomal miRNAomics analysis to explore the mechanism. We found that CSE-treated Beas-2B-derived exosomes could not only increase the percentages of CD86(+), CD80(+) CD163(+), and CD206 thorn cells but also induce the secretion of TNF-alpha, IL-6, iNOS, IL-10, Arg-1, and TGF-beta, indicating both M1 and M2 polarization of RAW264.7 macrophages were promoting. We performed miRNAomics analysis to identify 27 differentially expressed exosomal miRNAs such as miR-29a-3p and miR-1307-5p. Next, we obtained 14942 target genes of these miRNAs such as SCN1A and PLEKHA1 through the prediction of TargetScan and miRanda. We utilized KEGG enrichment analysis for these targets to identify potential pathways such as the PI3K-Akt signaling pathway and the MAPK signaling pathway on the regulation of macrophage polarization. We further found that miR-21-3p or miR-27b-3p may play critical roles in the promotion of CSE-Exo on macrophage polarization by miRNA interference. Collectively, this study provided novel information for diagnostic and therapeutic tactics of cigarette smoke-related lung diseases. (C) 2021 Elsevier Inc. All rights reserved.