Identification of exosome miRNAs in bronchial epithelial cells after PM2.5 chronic exposure

Zhong, Yingjie; Sun, Kunyan; Fan, Yong; Liao, Jiping; Wang, Guangfa

doi:10.1016/j.ecoenv.2021.112127

Cited by 20 publications

(6 citation statements)

References 38 publications

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“…Other recent reports have shown that miRNAs play an essential role in the occurrence and development of inflammatory airway diseases [ 31 , 32 ]. For instance, several studies have confirmed that environmental pollutants, including PM 2.5 , may alter the expression profile of miRNAs, resulting in pathogenic effects in humans [ 33 , 34 ]. In this study, we characterized the miRNA and mRNA transcriptomic profiles of mononuclear cells in the peripheral blood of COPD patients and observed the aberrant expression of multiple miRNA molecules in COPD.…”

Section: Discussionmentioning

confidence: 99%

MiR-23a-5p alleviates chronic obstructive pulmonary disease through targeted regulation of RAGE-ROS pathway

Chang,

Huang,

et al. 2024

Respir Res

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Background Chronic obstructive pulmonary disease (COPD) is a common respiratory disease and represents the third leading cause of death worldwide. This study aimed to investigate miRNA regulation of Receptor for Advanced Glycation End-products (RAGE), a causal receptor in the pathogenesis of cigarette smoke (CS)-related COPD, to guide development of therapeutic strategies. Methods RAGE expression was quantified in lung tissue of COPD patients and healthy controls, and in mice with CS-induced COPD. RNA-sequencing of peripheral blood from COPD patients with binding site prediction was used to screen differentially expressed miRNAs that may interact with RAGE. Investigation of miR-23a-5p as a potential regulator of COPD progression was conducted with miR-23a-5p agomir in COPD mice in vivo using histology and SCIREQ functional assays, while miR-23a-5p mimics or RAGE inhibitor were applied in 16-HBE human bronchial epithelial cells in vitro. RNA-sequencing, ELISA, and standard molecular techniques were used to characterize downstream signaling pathways in COPD mice and 16-HBE cells treated with cigarette smoke extract (CSE). Results RAGE expression is significantly increased in lung tissue of COPD patients, COPD model mice, and CSE-treated 16-HBE cells, while inhibiting RAGE expression significantly reduces COPD severity in mice. RNA-seq analysis of peripheral blood from COPD patients identified miR-23a-5p as the most significant candidate miRNA interaction partner of RAGE, and miR-23a-5p is significantly downregulated in mice and cells treated with CS or CSE, respectively. Injection of miR-23a-5p agomir leads to significantly reduced airway inflammation and alleviation of symptoms in COPD mice, while overexpressing miR-23a-5p leads to improved lung function. RNA-seq with validation confirmed that reactive oxygen species (ROS) signaling is increased under CSE-induced aberrant upregulation of RAGE, and suppressed in CSE-stimulated cells treated with miR-23a-5p mimics or overexpression. ERK phosphorylation and subsequent cytokine production was also increased under RAGE activation, but inhibited by increasing miR-23a-5p levels, implying that the miR-23a-5p/RAGE/ROS axis mediates COPD pathogenesis via ERK activation. Conclusions This study identifies a miR-23a-5p/RAGE/ROS signaling axis required for pathogenesis of COPD. MiR-23a-5p functions as a negative regulator of RAGE and downstream activation of ROS signaling, and can inhibit COPD progression in vitro and in vivo, suggesting therapeutic targets to improve COPD treatment. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

MiR-23a-5p alleviates chronic obstructive pulmonary disease through targeted regulation of RAGE-ROS pathway

Chang,

Huang,

et al. 2024

Respir Res

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“…For example, PCB quinonestimulated p-MLKL enhances exosome biogenesis and secretion (Peng et al, 2021). Chronic PM2.5 exposure causes bronchial epithelial cells to undergo atypical hyperplasia and induces the expression differences of miRNAs in exosome in vitro, which is partially associated with tumorigenesis (Wang et al, 2021). Therefore, we proposed that such variations may be caused by individual difference because of different health or physical conditions or because of low concentration limited by sequencing coverage.…”

Section: Isolation and Identification Exosomes From Hemolymph Of Pear...mentioning

confidence: 99%

Circulating exosome miRNAs, is it the connection cargo for cell communication and cross-kingdom communication by food chain in bivalves?

Zheng,

Cai,

Huang

et al. 2024

Preprint

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MicroRNAs (miRNAs) can efficiently regulate gene expression at intracellular and extracellular levels. Plant/food-derived miRNAs of the bio-environment are highly enriched in human serum or serum from phytophagous animals and play roles in the regulation of mammalian gene expression. However, the presence of food-derived miRNAs in Mollusca species is lacking evidence. In this study, we used the microalga Nannochloropsis oculata to feed the pearl oyster Pinctada fucata martensii, a bivalve species, and isolated exosomes from the serum to detect endogenous and food-derived miRNAs by RNA-seq. A total of 273 endogenous miRNAs were identified in all duplicate samples, and these participated in regulating cell proliferation and death, stress, energy metabolism, synthesis of unsaturated fatty acid, and protein synthesis and transport. Through the miRNA sequencing of the feeding N. oculata, we identified 23 microalga-derived miRNAs in the exosomes in the pearl oyster blood. Compared with endogenous miRNAs, most microalga-derived miRNAs showed high expression levels in both exosome and microalga cells and also exhibited apparent individual differences. These food-derived miRNAs were predicted to participate in endocytosis, apoptosis, signal transduction, energy metabolism, and biomineralization by targeting multiple genes. They were also closely related to energy metabolism and epigenetic regulation in N. oculata cells. These findings showed the phenomenon of cross-kingdom transport of miRNAs between a bivalve and feeding microalga and provided insights into functional molecule transmission through the food chain in an ecosystem.

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“…Animal and cell models suggest that EV might actively participate in the tumorigenesis induced by pollution. Wang and colleagues found that chronic PM2.5 exposure causes bronchial epithelial cells atypical hyperplasia and induces epithelial-to-mesenchymal transition in vivo, and identified a differential expression of miRNA exosomes in bronchial cell culture [56] providing a base for future studies in vivo.…”

Section: Ev In Lung Cancer Pathogenesismentioning

confidence: 99%

Extracellular Vesicles in Lung Cancer: Bystanders or Main Characters?

Tinè

Biondini

Damin

et al. 2023

Biology

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Lung cancer still represents the main cause of cancer death worldwide. The poor survival is mainly related to the diagnosis which is often obtained in advanced stages when the disease is unresectable and characterized by the worst prognosis. Only in the last decades have great discoveries led to the development of new therapies targeted to oncogenes and to boost the host immune response against the tumor. Tumor identification and molecular/immunological characterization rely on bioptic samples which represent the gold standard for diagnosis. Nonetheless, less invasive procedures providing small samples will be more and more common in the future. Extracellular vesicles (EV), submicron particles released by any cell type, are candidates for diagnostic and prognostic biomarkers. EV are mediators of intercellular communication and can convey cytokines, miRNAs, antigens, and many other factors of tumorigenesis. This review summarizes the most appealing findings on lung-cancer-related EV, debating the evidence on circulating versus airway EV as potential biomarkers in disease management and the main studies on the role of these particles on lung cancer pathogenesis. Overall, the available results point toward a wide range of possible applications, supported by the promising achievements of genotyping on BAL fluid EV and proteomic analysis on pleural effusion EV. Nonetheless, the study of lung EV is still affected by remarkable methodological issues, especially when in vitro evidence is translated into humans. Whether EV still represent an “information fog” or can be useful in lung cancer management will be discussed, with possible hints on how to improve their usage.

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Identification of exosome miRNAs in bronchial epithelial cells after PM2.5 chronic exposure

Cited by 20 publications

References 38 publications

MiR-23a-5p alleviates chronic obstructive pulmonary disease through targeted regulation of RAGE-ROS pathway

MiR-23a-5p alleviates chronic obstructive pulmonary disease through targeted regulation of RAGE-ROS pathway

Circulating exosome miRNAs, is it the connection cargo for cell communication and cross-kingdom communication by food chain in bivalves?

Extracellular Vesicles in Lung Cancer: Bystanders or Main Characters?

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