Plain-language summary
Pulmonary fibrosis is a progressive scarring disease of the lung in which activated fibroblasts deposit excess extracellular matrix, and current drugs such as pirfenidone and nintedanib only slow its course. This review examines how extracellular vesicles - tiny membrane-bound particles that ferry microRNAs, proteins, and lipids between cells - shape that process in two opposing ways. On the harmful side, vesicles released by injured epithelial and immune cells carry pro-fibrotic microRNAs such as miR-494-3p, which amplify TGF-beta/Smad and Wnt signalling and drive fibroblasts toward the matrix-producing myofibroblast state. On the protective side, vesicles from mesenchymal stem cells have shown anti-fibrotic activity in preclinical models by rebalancing the same pathways, steering macrophages toward a resolving phenotype, and supporting mitochondrial function; an early-phase study of nebulized administration has reported initial safety data. The authors also survey vesicles found in plasma, sputum, and urine as candidate biomarkers, and outline the remaining obstacles: cargo standardization, targeted delivery, and large-scale manufacturing.
Key findings
- Epithelial- and immune-cell-derived extracellular vesicles can carry pro-fibrotic microRNAs such as miR-494-3p that activate TGF-beta/Smad and Wnt/beta-catenin signalling in pulmonary fibrosis.
- Mesenchymal stem cell-derived vesicles show anti-fibrotic effects in preclinical models by modulating the same signalling pathways, macrophage polarization, and mitochondrial function.
- A phase I study has provided initial safety evidence for nebulized vesicle administration, but therapeutic efficacy in pulmonary fibrosis is not yet established.
- Vesicles isolated from plasma, bronchoalveolar lavage fluid, sputum, and urine carry molecular signatures that may become diagnostic or monitoring biomarkers pending clinical validation.
Original abstract
Pulmonary fibrosis (PF) is a progressive interstitial lung disease driven by excessive fibroblast activation and extracellular matrix (ECM) deposition, for which pirfenidone and nintedanib slow but do not halt disease progression. Extracellular vesicles (EVs)-lipid bilayer-enclosed nanoparticles that shuttle microRNAs (miRNAs), proteins, and lipids between cells-are increasingly recognized as important mediators and potential modulators of fibrotic remodeling. On the pathogenic side, epithelial- and immune-cell-derived EVs can deliver pro-fibrotic miRNAs (e.g., miR-494-3p) that regulate transforming growth factor beta (TGF-β)/Smad and Wnt/β-catenin signaling, promoting fibroblast-to-myofibroblast transition and ECM accumulation. Conversely, selected mesenchymal stem cell-derived EV (MSC-EV) preparations have demonstrated anti-fibrotic effects in preclinical models through modulation of TGF-β/Smad signaling, M2 macrophage polarization, mitochondrial function, and epithelial-mesenchymal transition; a phase I clinical study has provided initial safety evidence for nebulized administration, although therapeutic efficacy in PF has not yet been established. Beyond MSC-EVs, plant-derived and milk-derived EVs have emerged as potential delivery platforms, although their applications remain largely preclinical. Meanwhile, EVs isolated from plasma, bronchoalveolar lavage fluid, sputum, and urine carry disease-associated molecular signatures that may serve as candidate biomarkers for PF detection or monitoring, but require further clinical validation. This review synthesizes recent evidence on the dual roles of EVs in PF pathogenesis and therapy, evaluates their potential diagnostic utility, and discusses translational hurdles-including cargo standardization, targeted delivery, and scalable manufacturing-that must be overcome for clinical adoption.
Frequently asked questions
What did this study find?
Pulmonary fibrosis is a progressive scarring disease of the lung in which activated fibroblasts deposit excess extracellular matrix, and current drugs such as pirfenidone and nintedanib only slow its course. This review examines how extracellular vesicles - tiny membrane-bound particles that ferry microRNAs, proteins, and lipids between cells - shape that process in two opposing ways. On the harmful side, vesicles released by injured epithelial and immune cells carry pro-fibrotic microRNAs such as miR-494-3p, which amplify TGF-beta/Smad and Wnt signalling and drive fibroblasts toward the matrix-producing myofibroblast state. On the protective side, vesicles from mesenchymal stem cells have shown anti-fibrotic activity in preclinical models by rebalancing the same pathways, steering macrophages toward a resolving phenotype, and supporting mitochondrial function; an early-phase study of nebulized administration has reported initial safety data. The authors also survey vesicles found in plasma, sputum, and urine as candidate biomarkers, and outline the remaining obstacles: cargo standardization, targeted delivery, and large-scale manufacturing.
Was this tested in humans or in the laboratory?
This is a review: it summarises and weighs up previously published studies rather than presenting new experiments.
Where can I read the original paper?
The full text lives with the publisher: https://doi.org/10.1007/s11033-026-12858-9
How to cite this paper
Liu Xinyi, Zhao Zhenzhen, Zhu Lijuan, Zhang Wen, Zhou Jinhan, Wu Xiaodan et al.. How extracellular vesicles contribute to pulmonary fibrosis: miRNA-mediated mechanisms, diagnostic potential, and emerging therapeutic strategies.. Molecular biology reports. 2026, 2026-10-01. DOI: 10.1007/s11033-026-12858-9
Source & verification
- Journal: Molecular biology reports
- Published: 1 October 2026
- DOI: 10.1007/s11033-026-12858-9
- PubMed ID: 42821136
- Indexed via: pubmed
- MeSH terms: Humans, Extracellular Vesicles, MicroRNAs, Pulmonary Fibrosis, Animals, Mesenchymal Stem Cells, Transforming Growth Factor beta, Signal Transduction