M2 macrophage-derived extracellular vesicles (EVs) miR-155-5p promotes pulmonary fibrosis via epithelial-mesenchymal transition in lung epithelial cells.

Authors

Shuhong Guan, Ying Ding, Tianyu Chen, Junkang Huangfu, Long Zhang, Xiyao Chen, Jun Zhou

Published in

Molecular biology reports. Volume 53. Issue 1. Jul 28, 2026. Epub Jul 28, 2026.

Abstract

Pulmonary fibrosis (PF) is a progressive and irreversible interstitial lung disease characterized by excessive extracellular matrix deposition and epithelial-mesenchymal transition (EMT). Increasing evidence indicates that macrophage-derived extracellular vesicles (EVs) are involved in fibrotic remodeling; however, the role of M2 macrophage-derived EV-associated miR-155-5p in PF remains unclear.
EVs were isolated from M0 and IL-4-induced M2 macrophages and characterized by transmission electron microscopy, nanoparticle tracking analysis, and immunoblotting. Differential miRNA sequencing revealed that miR-155-5p was significantly enriched in M2 macrophage-derived EVs. Fluorescence imaging confirmed the uptake of EVs by MLE-12 cells. Functional analyses demonstrated that M2 EVs promoted EMT in MLE-12 cells, as evidenced by increased expression of Vimentin, α-SMA, Snail, Slug, Twist, and Zeb1, along with decreased E-cadherin expression. Inhibition of miR-155-5p reversed these EMT-associated changes. Luciferase reporter assays and rescue experiments further demonstrated that miR-155-5p directly targeted FOXO3a and SHIP-1. In vivo, bleomycin-induced PF mice treated with M2 macrophage-derived EVs exhibited aggravated pulmonary fibrosis, increased collagen deposition, and enhanced EMT marker expression, whereas treatment with miR-155-5p inhibitor-transfected EVs significantly alleviated fibrotic progression. Moreover, M2 macrophage-derived EVs exhibit favorable biosafety and preferential pulmonary accumulation in vivo.
M2 macrophage-derived EVs-associated miR-155-5p promotes pulmonary fibrosis progression by enhancing EMT through the FOXO3a/SHIP-1-associated signaling axis. Targeting EV-delivered miR-155-5p may represent a potential therapeutic strategy for pulmonary fibrosis.

PMID:
42517936
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.

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