Epithelial‑derived exosomes promote M2 macrophage polarization via Notch2/SOCS1 during mechanical ventilation

Wang,Yanting; Wang,Yanting; Xie,Wanli; Xie,Wanli; Feng,Yiqi; Feng,Yiqi; Xu,Zhenzhen; Xu,Zhenzhen; He,Yuyao; He,Yuyao; Xiong,Yue; Xiong,Yue; Chen,Lu; Chen,Lu; Li,Xia; Li,Xia; Liu,Jie; Liu,Jie; Liu,Guoyang; Liu,Guoyang; Wu,Qingping; Wu,Qingping

doi:10.3892/ijmm.2022.5152

Epithelial‑derived exosomes promote M2 macrophage polarization via Notch2/SOCS1 during mechanical ventilation

Authors:
- Yanting Wang
- Wanli Xie
- Yiqi Feng
- Zhenzhen Xu
- Yuyao He
- Yue Xiong
- Lu Chen
- Xia Li
- Jie Liu
- Guoyang Liu
- Qingping Wu
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Affiliations: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China
Published online on: May 25, 2022 https://doi.org/10.3892/ijmm.2022.5152
Article Number: 96
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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