Extracellular Vesicles in the Respiratory System: The Prominent Role of miRNAs in Pathophysiology, Diagnostics, and Therapeutics.
4 affiliations
- 1Department of Pharmacy, The People's Hospital of Cangnan, Wenzhou, Zhejiang, 325800, People's Republic of China.
- 2Pharmacology of the Ministry of Education and Joint International Research Laboratory of Ethnomedicine of the Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, People's Republic of China.
- 3The First Clinical College, Chongqing Medical University, Chongqing, People's Republic of China.
- 4Department of Orthopaedic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Abstract
Extracellular vesicles (EVs) are lipid-bilayer particles that mediate intercellular communication by transferring proteins, lipids, nucleic acids, and metabolites. Their molecular composition reflects both cellular origin and disease state, creating opportunities for mechanistic studies, liquid-biopsy biomarkers, and cell-free therapeutics in respiratory medicine. We critically synthesize EV-mediated regulation across chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis (PF), lung cancer, and respiratory infections, with attention to clinically relevant phenotypes and endotypes. Rather than cataloguing differential cargo alone, we focus on causal signaling networks involving TGF-β/Smad, NF-kB/NLRP3, PI3K/Akt/mTOR, MAPK, JAK/STAT, and Wnt/β-catenin pathways. We further evaluate EV biomarkers according to biofluid source, isolation strategy, disease subtype, diagnostic performance, and requirements for external validation. Native and engineered EV therapeutics are discussed together with pulmonary delivery, biodistribution, and early clinical evidence. Importantly, promising preclinical findings are tempered by major translational barriers, including EV heterogeneity, non-uniform isolation and characterization, uncertain dose metrics and potency assays, rapid clearance or off-target sequestration, manufacturing scalability, storage stability, long-term safety, and evolving regulatory expectations. Future progress will require MISEV-aligned standardization, mechanistic perturbation and rescue experiments, single-EV and organoid/lung-on-chip models, prospective multicenter biomarker validation, and GMP-compatible manufacturing. These advances are essential to move respiratory EV research from descriptive associations toward reproducible mechanisms and clinically actionable diagnostics and therapeutics.
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BibTeX
@article{ling2026extracellular,
title = {{Extracellular Vesicles in the Respiratory System: The Prominent Role of miRNAs in Pathophysiology, Diagnostics, and Therapeutics.}},
author = {Hong Ling and Hong Xiao and Zejian Zhong and Xinhang Li and Qiaotian Yin and Meipei Gao and Wei Huang and Meng Zhang and Qiming Pang},
journal = {International journal of nanomedicine},
year = {2026},
month = nov,
doi = {10.2147/ijn.s632138},
url = {https://europepmc.org/article/MED/42999631},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Extracellular Vesicles in the Respiratory System: The Prominent Role of miRNAs in Pathophysiology, Diagnostics, and Therapeutics.
AU - Hong Ling
AU - Hong Xiao
AU - Zejian Zhong
AU - Xinhang Li
AU - Qiaotian Yin
AU - Meipei Gao
AU - Wei Huang
AU - Meng Zhang
AU - Qiming Pang
PY - 2026
DA - 2026/11/03
JO - International journal of nanomedicine
DO - 10.2147/ijn.s632138
UR - https://europepmc.org/article/MED/42999631
AB - Extracellular vesicles (EVs) are lipid-bilayer particles that mediate intercellular communication by transferring proteins, lipids, nucleic acids, and metabolites. Their molecular composition reflects both cellular origin and disease state, creating opportunities for mechanistic studies, liquid-biopsy biomarkers, and cell-free therapeutics in respiratory medicine. We critically synthesize EV-mediated regulation across chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis (PF), lung cancer, and respiratory infections, with attention to clinically relevant phenotypes and endotypes. Rather than cataloguing differential cargo alone, we focus on causal signaling networks involving TGF-β/Smad, NF-kB/NLRP3, PI3K/Akt/mTOR, MAPK, JAK/STAT, and Wnt/β-catenin pathways. We further evaluate EV biomarkers according to biofluid source, isolation strategy, disease subtype, diagnostic performance, and requirements for external validation. Native and engineered EV therapeutics are discussed together with pulmonary delivery, biodistribution, and early clinical evidence. Importantly, promising preclinical findings are tempered by major translational barriers, including EV heterogeneity, non-uniform isolation and characterization, uncertain dose metrics and potency assays, rapid clearance or off-target sequestration, manufacturing scalability, storage stability, long-term safety, and evolving regulatory expectations. Future progress will require MISEV-aligned standardization, mechanistic perturbation and rescue experiments, single-EV and organoid/lung-on-chip models, prospective multicenter biomarker validation, and GMP-compatible manufacturing. These advances are essential to move respiratory EV research from descriptive associations toward reproducible mechanisms and clinically actionable diagnostics and therapeutics.
SN - 1176-9114
SN - 1178-2013
ER -