Table 4.

Summary of studies on EVs containing miRNA in COPD

Mechanism—microRNA
Author, year [Ref.]	Title	Aim	Type	Conclusion
He et al., 2019 [36]	Bronchial epithelial cells extracellular vesicles ameliorate epithelial–mesenchymal transition in COPD pathogenesis by alleviating M2 macrophage polarization	Investigate whether EVs could influence the occurrence of inflammatory lung disease (in particular COPD) through contained microRNAs	In vitro Ex vivo human In vivo Mice	EVs found in the serum contained significantly higher levels of miR-21 in COPD patients than healthy people. CS was found to reduce levels of miR-21 in EVs of BEAS-2B cells at 1%, 3% and 5% when compared to 0%. Macrophages were then found to uptake these EVs, resulting in polarization into M2 phenotype which negatively correlated with lung function of mouse COPD models
Xu et al., 2018 [37]	Exosomal microRNA-21 derived from bronchial epithelial cells is involved in aberrant epithelium-fibroblast cross-talk in COPD induced by cigarette smoking	Evaluate the expression of miR-21 in exosomes derived from bronchial epithelial cells exposed to CSE and investigate the mechanism for exosomal miR-21 in airway remodeling	In vitro Ex vivo Human In vivo Mice	CS exposure induces increases of miR-21 levels transferred by exosomes from human bronchial epithelial (HBE) cells into bronchial fibroblast cells, promoting myofibroblast differentiation by increases of HIF-1a transcriptional activity
Fujita et al., 2015 [38]	Suppression of autophagy by extracellular vesicles promotes myofibrobasts differentiation in COPD pathogenesis	Investigate an EV-mediated intercellular communication mechanism between primary human bronchial epithelial cells (HBECs) and lung fibroblasts (LFs)	In vitro	CSE-induced HBEC derived EVs had modified components, 8 miRNAs including miR-210, when compared to non-treated HBEC-derived EVs. HBEC-derived EV miR-210 caused significant increase in collagen type I and a-SMA expression in lung fibroblasts (LFs) which are characteristic of myofibroblast differentiation via EVs
Serban et al., 2016 [39]	Structural and functional characterization of endothelial microparticles released by cigarette smoke	Investigate the role of signaling of pathways typically involved in endothelial apoptosis in EMPs release and the role of CS-induced EMPs and their impact on specialized phagocytes	In vitro Ex vivo Human In vivo/ex vivo mice	CS, via aSMase, releases circulating EMPs with distinct microRNA cargo. CS-induced apoptotic and exosomal EMPs carry ceramides and specific miRNAs in circulation and result in interference of efferocytosis