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YAP Deficiency Attenuates Pulmonary Injury Following Mechanical Ventilation Through the Regulation of M1/M2 Macrophage Polarization
Journal of Inflammation Research ( IF 4.2 ) Pub Date : 2020-12-31 , DOI: 10.2147/jir.s288244
Qiong Luo 1 , Jing Luo 1 , Yanlin Wang 1
Affiliation  

Background: Evidences indicate that the balance between macrophage M1 and M2 polarization is essential for the regulation of pulmonary inflammation during mechanical ventilation (MV). Yes-associated protein (YAP) is a key component of the Hippo pathway and was suggested to regulate macrophage polarization. This study was designed to investigate whether YAP contributes to pulmonary inflammation during MV.
Methods: Wild-type and macrophage YAP knockout mice were mechanically ventilated for 12 hours to induce pulmonary injuries. At the end of MV, animals were sacrificed for pulmonary tissue collection and macrophage isolation. In addition, the induction of macrophage polarization was performed in isolated macrophages with or without YAP overexpression in vitro. Pulmonary injuries, YAP expression, macrophage polarization and cytokines were measured.
Results: Here, we show that MV induces lung injury together with pulmonary inflammation as well as upregulated YAP expressions in pulmonary macrophages. In addition, our results indicate that YAP deficiency in macrophages attenuates pulmonary injury, accompanied with decreased production of pro-inflammatory cytokines including IL (interleukin)-1β, IL-6 and tumor necrosis factor-alpha (TNF-α). Moreover, both in vivo and in vitro studies indicate that YAP deficiency enhances M2 polarization while inhibits M1 polarization. In contrast, YAP overexpression inhibits the induction of M2 polarization but improves M1 polarization.
Conclusion: Our results report for the first time that the induction of YAP in macrophages contributes to pulmonary inflammation during MV through the regulation of M1/M2 polarization.



中文翻译:

YAP 缺乏通过调节 M1/M2 巨噬细胞极化减轻机械通气后的肺损伤

背景:有证据表明,巨噬细胞 M1 和 M2 极化之间的平衡对于机械通气 (MV) 期间肺部炎症的调节至关重要。Yes 相关蛋白 (YAP) 是 Hippo 通路的关键组成部分,被认为可调节巨噬细胞极化。本研究旨在调查 YAP 是否有助于 MV 期间的肺部炎症。
方法:野生型和巨噬细胞 YAP 敲除小鼠机械通气 12 小时以诱导肺损伤。在 MV 结束时,处死动物进行肺组织收集和巨噬细胞分离。此外,在体外有或没有 YAP 过表达的孤立巨噬细胞中进行巨噬细胞极化的诱导。测量肺损伤、YAP 表达、巨噬细胞极化和细胞因子。
结果:在这里,我们显示 MV 与肺部炎症一起诱导肺损伤以及肺巨噬细胞中 YAP 表达上调。此外,我们的研究结果表明,巨噬细胞中的 YAP 缺乏会减轻肺损伤,并伴有包括 IL(白细胞介素)-1β、IL-6 和肿瘤坏死因子-α(TNF-α)在内的促炎细胞因子的产生减少。此外,体内和体外研究表明,YAP 缺乏会增强 M2 极化,同时抑制 M1 极化。相比之下,YAP 过表达抑制了 M2 极化的诱导,但改善了 M1 极化。
结论:我们的研究结果首次报道了巨噬细胞中 YAP 的诱导通过调节 M1/M2 极化促进了 MV 期间的肺部炎症。

更新日期:2020-12-31
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