Department of Respiratory Medicine, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Prevention and Health Care Department of TCM, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Aging (Albany NY). 2022 May 2;14(9):3921-3940. doi: 10.18632/aging.204053.
Asthma is one of the most common chronic inflammatory diseases. Although the scorpion and centipede (SC) significantly ameliorates asthma and changes exosomal miRNAs, the molecular mechanism is still obscure. Here, we show that SC improves inflammation in asthmatic mice and increases M2 macrophage-derived exosomes (M2Φ-Exos) by promoting M2 macrophage polarization. The M2Φ-Exos remarkably inhibits airway epithelial cell pyroptosis by reducing the expression of NLRP3, caspase-1, and LI-1β and mitochondrial swelling. Furthermore, miR-30b-5p is up-regulated in M2Φ-Exos compared with M1Φ-Exos. Overexpression of miR-30b-5p in M2Φ-Exos prevents airway epithelial cell pyroptosis, while down-regulation of miR-30b-5p promotes pyroptosis. We also uncover that pyroptosis is increased in asthmatic mice, while SC blocks pyroptosis. Moreover, miR-30b-5p overexpressed M2Φ-Exos further enhances the ameliorative effect of SC, which significantly down-regulates IRF7 expression. Our results collectively reveal that M2Φ-Exos induced by SC could carry miR-30b-5p to mitigate severe asthma by inhibiting airway epithelial cell pyroptosis. Most importantly, our findings may provide a potential clinical application of M2Φ-Exos for treating severe asthma.
哮喘是最常见的慢性炎症性疾病之一。尽管蝎子和蜈蚣（SC）能显著改善哮喘并改变外泌体 miRNAs，但分子机制仍不清楚。在这里，我们表明 SC 通过促进 M2 巨噬细胞极化来改善哮喘小鼠的炎症并增加 M2 巨噬细胞衍生的外泌体（M2Φ-Exos）。M2Φ-Exos 通过降低 NLRP3、caspase-1 和 LI-1β 的表达以及线粒体肿胀来显著抑制气道上皮细胞焦亡。此外，与 M1Φ-Exos 相比，M2Φ-Exos 中 miR-30b-5p 的表达上调。M2Φ-Exos 中 miR-30b-5p 的过表达可防止气道上皮细胞焦亡，而 miR-30b-5p 的下调则促进焦亡。我们还发现哮喘小鼠中焦亡增加，而 SC 阻止焦亡。此外，过表达 miR-30b-5p 的 M2Φ-Exos 进一步增强了 SC 的改善作用，从而显著下调了 IRF7 的表达。我们的研究结果表明，SC 诱导的 M2Φ-Exos 可以通过抑制气道上皮细胞焦亡来携带 miR-30b-5p 来减轻严重哮喘。最重要的是，我们的发现可能为治疗严重哮喘提供了 M2Φ-Exos 的潜在临床应用。
