Epithelial‑derived exosomes promote M2 macrophage polarization via Notch2/SOCS1 during mechanical ventilation
Epithelial‑derived exosomes promote M2 macrophage polarization via Notch2/SOCS1 during mechanical ventilation
复制标题
机械通气期间上皮衍生的外泌体通过 Notch2/SOCS1 促进 M2 巨噬细胞极化
DOI：
10.3892/ijmm.2022.5152
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Qingping Wu
中科院分区：
文献类型：
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作者：
Yanting Wang;Wanli Xie;Yiqi Feng;Zhenzhen Xu;Yuyao He;Yue Xiong;Lu Chen;Xia Li;Jie Liu;Guoyang Liu;Qingping Wu
肺泡巨噬细胞（AM）在呼吸机诱导的肺损伤（VILI）中发挥重要作用。外来体及其货物，包括microRNA（miRNA/miR），作为巨噬细胞和上皮细胞（EC）之间的细胞间通讯的调节剂，并参与维持肺组织中的稳态。本研究发现，由经历循环拉伸的EC释放的外泌体促进M2巨噬细胞极化。研究表明，在上皮来源的外泌体中上调的miR-21 a-5 p通过抑制Notch 2和细胞因子信号转导抑制因子1（SOCS 1）的表达来增加M2巨噬细胞的百分比。Notch 2的过表达降低了M2巨噬细胞的百分比。然而，这些作用被SOCS 1的下调逆转。M2巨噬细胞的百分比在短期高潮气量和低潮气量机械通气中均增加，并且来自周期性拉伸EC的外泌体的施用具有相同的功能。然而，miR-21 a-5 p的给药降低了由周期性伸展的EC或通气诱导的M2巨噬细胞活化。因此，本研究表明，外泌体从EC到AM的细胞间转移促进了M2巨噬细胞极化。外泌体可能被证明是VILI的一种新疗法。
Alveolar macrophages (AMs) play an essential role in ventilator‑induced lung injury (VILI). Exosomes and their cargo, including microRNAs (miRNAs/miRs) serve as regulators of the intercellular communications between macrophages and epithelial cells (ECs), and are involved in maintaining homeostasis in lung tissue. The present study found that exosomes released by ECs subjected to cyclic stretching promoted M2 macrophage polarization. It was demonstrated that miR‑21a‑5p, upregulated in epithelial‑derived exosomes, increased the percentage of M2 macrophages by suppressing the expression of Notch2 and the suppressor of cytokine signaling 1 (SOCS1). The overexpression of Notch2 decreased the percentage of M2 macrophages. However, these effects were reversed by the downregulation of SOCS1. The percentage of M2 macrophages was increased in both short‑term high‑ and low‑tidal‑volume mechanical ventilation, and the administration of exosomes‑derived from cyclically stretched ECs had the same function. However, the administration of miR‑21a‑5p antagomir decreased M2 macrophage activation induced by cyclically stretched ECs or ventilation. Thus, the present study demonstrates that the intercellular transferring of exosomes from ECs to AMs promotes M2 macrophage polarization. Exosomes may prove to be a novel treatment for VILI.