M2 macrophage-derived exosomes reverse TGF-β1-induced epithelial mesenchymal transformation in BEAS-2B cells via the TGF-βRI/Smad2/3 signaling pathway

被引：0

作者：

Liu, Chao ^{[1
]}

Huang, Xiaolin ^{[2
]}

Li, Siqi ^{[1
]}

Ji, Wentao ^{[1
]}

Luo, Tian ^{[1
]}

Liang, Jianping ^{[1
]}

Lv, Yanhua ^{[3
]}

机构：

[1] Zhongshan Peoples Hosp, Dept Resp & Crit Care Med, Zhongshan, Guangdong, Peoples R China

[2] Zhongshan Stomatol Hosp, Dent Implant & Restorat Ctr, Zhongshan, Guangdong, Peoples R China

[3] Southern Med Univ, Shunde Hosp, First Peoples Hosp Shunde, Dept Resp & Crit Care Med, Foshan, Guangdong, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICAL RESEARCH | 2025年 / 30卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Macrophages; Exosomes; Epithelial mesenchymal transformation; Airway epithelial cells; Airway remodeling;

D O I：

10.1186/s40001-025-02516-4

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

IntroductionAirway remodeling in bronchial asthma can be inhibited by disrupting the epithelial mesenchymal transition (EMT) of activated airway epithelial cells. Exosomes, as key mediators of intercellular communication, have been implicated in the pathophysiology of asthma-related airway inflammation, remodeling, and hyperresponsiveness. This study aimed to investigate the role of M2 macrophage-derived exosomes (M2 phi-exos) in modulating TGF-beta 1-induced EMT in airway epithelial (BEAS-2B) cells and elucidate the underlying molecular mechanism, if any.MethodsTHP-1 cells were induced to differentiate into M2 macrophages via phorbol 12-myristate 13-acetate (PMA) and IL-4. Exosomes were subsequently isolated and purified via ultracentrifugation. M2 phi-exos expression was characterized by protein marker levels, transmission electron microscopy imaging, and nanoparticle tracking analysis. TGF-beta 1-induced BEAS-2B cells were exposed to M2 phi-exos to determine the latter's effects.ResultsTHP-1 cells were successfully differentiated into M2 macrophages, as confirmed by in vitro flow cytometry. The isolated exosomes presented typical cup-shaped structures and expressed CD81 and TSG101. TGF-beta 1 induction altered the morphological characteristics of BEAS-2B cells and activated the TGF-beta RI/Smad2/3 signaling pathway, leading to increased expression of Snail, Vimentin and Collagen 1 and decreased expression of E-cadherin. After exosome or SB431542 induction, TGF-beta 1-induced EMT was reversed. GW4869, an exosome release inhibitor, exhibited the ability to block the beneficial effects of exosomes.ConclusionM2 Phi-exos inhibited EMT in BEAS-2B cells through the TGF-beta RI/Smad2/3 signaling pathway. This novel insight into the role of M2 Phi-exos in modulating EMT may have important implications for the beneficial effects of asthma, particularly in addressing airway remodeling.

引用

页数：15

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