Abstract：
Numerous studies have shown that the M2 polarization of alveolar macrophages (AM) plays a protective role in acute lung injury (ALI). Mesenchymal stem cells (MSCs) secreted exosomes have been reported to be involved in inflammatory diseases by the effects of polarized M1/M2 macrophage populations. However, whether bone marrow mesenchymal stem cells (BMMSCs) derived exosomes could protect from ALI and its mechanisms are still unclear. Here, we explored the role of exosomes from BMMSC in rat AM polarization and the lipopolysaccharide- (LPS-) induced ALI rat model. Furthermore, the levels of exosomal miR-223 in BMMSCs were measured by RT-qPCR. Additionally, miR-223 mimics and its inhibitors were used to verify the vital role of miR-223 of BMMSCs-derived exosomes in the polarization of M2 macrophages. The results showed that BMMSCs-derived exosomes were taken up by the AM. Exosomes derived from BMMSCs promoted M2 polarization of AM in vitro. BMMSCs exosomes effectively mitigated pathological injuries, lung edema, and the inflammation of rats from LPS-induced ALI, accompanied by an increase of M2 polarization of AM in lung tissue. Interestingly, we also found that miR-223 was enriched in BMMSCs-derived exosomes, and overexpression of miR-223 in BMMSCs-derived exosomes promoted M2 polarization of AM while depressing miR-223 showed opposite effects in AM. The present study demonstrated that BMMSCs-derived exosomes triggered alveolar M2 polarization to improve inflammation by transferring miR-223, which may provide new therapeutic strategies in ALI.
摘要：
大量研究表明，肺泡巨噬细胞（AM）的M2极化在急性肺损伤（ALI）中起保护作用。据报道，间充质干细胞（MSCs）分泌的外泌体通过极化的M1/M2巨噬细胞群的作用参与炎症性疾病。然而,骨髓间充质干细胞（BMMSCs）来源的外泌体是否可以预防ALI及其机制尚不清楚。这里,我们探讨了BMMSC的外泌体在大鼠AM极化和脂多糖（LPS）诱导的ALI大鼠模型中的作用。此外，通过RT-qPCR检测BMMSCs中外泌体miR-223的水平。此外,miR-223模拟物及其抑制剂用于验证BMMSCs来源的外泌体miR-223在M2巨噬细胞极化中的重要作用。结果表明，BMMSCs来源的外泌体被AM吸收。BMMSCs来源的外泌体在体外促进AM的M2极化。BMMSCs外泌体有效减轻病理损伤，肺水肿,和LPS诱导的ALI大鼠的炎症，伴随着肺组织中AM的M2极化增加。有趣的是,我们还发现miR-223在BMMSCs来源的外泌体中富集，miR-223在BMMSCs来源的外泌体中的过表达可促进AM的M2极化，而miR-223的抑制在AM中显示出相反的作用。本研究表明，BMMSCs来源的外泌体通过转移miR-223触发肺泡M2极化改善炎症，这可能为ALI提供新的治疗策略。
