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

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

  • Eur J Med Res. 2025 Apr 11;30(1):271. doi: 10.1186/s40001-025-02516-4.
Chao Liu # 1,  Xiaolin Huang # 2,  Siqi Li 1,  Wentao Ji 1,  Tian Luo 1,  Jianping Liang 3,  Yanhua Lv 4
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, Zhongshan People's Hospital, Zhongshan, Guangdong, China.
  • 2 Dental Implant and Restoration Centre, Zhongshan Stomatological Hospital, Zhongshan, Guangdong, China.
  • 3 Department of Respiratory and Critical Care Medicine, Zhongshan People's Hospital, Zhongshan, Guangdong, China. 18070376761@163.com.
  • 4 Department of Respiratory and Critical Care Medicine, Shunde Hospital, Southern Medical University (the First People'S Hospital of Shunde), Foshan, Guangdong, China. lyhshunde@163.com.
  • # Contributed equally.
PMID: 40211426 DOI: 10.1186/s40001-025-02516-4
Abstract

Introduction: Airway 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 (M2φ-exos) in modulating TGF-β1-induced EMT in airway epithelial (BEAS-2B) cells and elucidate the underlying molecular mechanism, if any.

Methods: THP-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. M2φ-exos expression was characterized by Protein Marker levels, transmission electron microscopy imaging, and nanoparticle tracking analysis. TGF-β1-induced BEAS-2B cells were exposed to M2φ-exos to determine the latter's effects.

Results: THP-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-β1 induction altered the morphological characteristics of BEAS-2B cells and activated the TGF-βRI/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-β1-induced EMT was reversed. GW4869, an exosome release inhibitor, exhibited the ability to block the beneficial effects of exosomes.

Conclusion: M2Φ-exos inhibited EMT in BEAS-2B cells through the TGF-βRI/SMAD2/3 signaling pathway. This novel insight into the role of M2Φ-exos in modulating EMT may have important implications for the beneficial effects of asthma, particularly in addressing airway remodeling.

Keywords

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

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