Department of Respiratory Medicine, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Internal Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Biomed Res Int. 2020 Jan 16;2020:1061407. doi: 10.1155/2020/1061407. eCollection 2020.
Asthma is a common respiratory disease with inflammation in the lungs. Exosomes and microRNAs (miRNAs) play crucial role in inflammation, whereas the role of exosomal miRNA in asthma remains unknown. Here, we aimed to identify the key exosomal miRNAs and their underlying mechanisms involved in scorpio and centipede (SC) treatment in asthma. Eighteen mice were randomly divided into three groups: control group, asthma group, and SC treatment group. Effect of SC was assessed by hematoxylin-eosin staining and real-time PCR. Exosomes from asthma and SC treatment groups were analyzed by small RNA-seq. Results revealed SC significantly alleviated the pathogenesis of asthma and suppressed the release of inflammatory cytokines. A total of 328 exosomal miRNAs were differentially expressed between the exosomes from asthma and SC-treated mice, including 118 up- and 210 downregulated in SC-treated mice. The altered exosomal miRNAs were primarily involved in the function of transcription, apoptotic process, and cell adhesion; and pathway of calcium, Wnt, and MAPK signaling. Real-time PCR verified exosomal miR-147 was downregulated, while miR-98-5p and miR-10a-5p were upregulated in SC-treated mice compared to asthma mice. Moreover, the target genes of miR-147-3p, miR-98-5p, and miR-10a-5p were mainly enriched in Wnt and MAPK inflammatory signaling. miR-10a-5p promoted the proliferation of mouse lung epithelial cells and downregulated the expression of Nfat5 and Map2k6. These data suggest SC-induced exosomal miRNAs might mediate the inflammatory signaling and might be involved in the SC treatment in asthma. The exosomal miRNAs might be promising candidates for the treatment of asthma.
哮喘是一种常见的肺部炎症性呼吸道疾病。外泌体和 microRNAs(miRNAs)在炎症中发挥关键作用,而外泌体 miRNA 在哮喘中的作用尚不清楚。在这里,我们旨在鉴定在蝎子和蜈蚣(SC)治疗哮喘中起关键作用的外泌体 miRNA 及其潜在机制。将 18 只小鼠随机分为三组:对照组、哮喘组和 SC 治疗组。通过苏木精-伊红染色和实时 PCR 评估 SC 的作用。通过小 RNA-seq 分析哮喘和 SC 治疗组的外泌体。结果表明,SC 显著缓解了哮喘的发病机制并抑制了炎症细胞因子的释放。哮喘和 SC 治疗组的外泌体之间有 328 个差异表达的外泌体 miRNA,其中在 SC 治疗组中 118 个上调,210 个下调。改变的外泌体 miRNA 主要参与转录、凋亡过程和细胞黏附;以及钙、Wnt 和 MAPK 信号通路。实时 PCR 验证了与哮喘小鼠相比,SC 治疗组的外泌体 miR-147 下调,而 miR-98-5p 和 miR-10a-5p 上调。此外,miR-147-3p、miR-98-5p 和 miR-10a-5p 的靶基因主要富集在 Wnt 和 MAPK 炎症信号中。miR-10a-5p 促进了小鼠肺上皮细胞的增殖,并下调了 Nfat5 和 Map2k6 的表达。这些数据表明,SC 诱导的外泌体 miRNA 可能介导炎症信号,并可能参与 SC 治疗哮喘。外泌体 miRNA 可能是治疗哮喘的有前途的候选物。