Trends in Molecular Medicine
ReviewExtracellular vesicles in lung microenvironment and pathogenesis
Section snippets
Secreted vesicles and intercellular communication in the airway microenvironment
Lung diseases are an increasingly important factor in morbidity and mortality rates worldwide. The high incidence of these diseases generally results from inhalation of air pollution, infectious agents, and various toxic antigens with concomitant immune responses. Airway injury from exposure to cigarette smoke and other air pollutants is a major risk factor in the development of various lung diseases, including lung cancer, pulmonary fibrosis, asthma, and COPD. In healthy subjects, bronchial
EV classification and biogenesis
EVs were originally described in 1983 in the laboratory of Rose Johnstone [14]. Currently, a growing body of evidence shows that the production of EVs is a universal feature of cellular biological functions. EVs can be detected in cell culture supernatants and in various biological fluids such as blood, urine, sputum, BAL fluid, synovial fluid, pleural effusions, breast milk, and ascites [15]. The main classes of EVs generally include exosomes, microvesicles (also referred to as ectosomes and
Homeostatic role of EVs in normal airway physiology
Given their isolation from normal extracellular fluids 15, 24, EVs are likely to play important roles in normal lung physiology to maintain homeostasis through intercellular communication in the human airway (Figure 3). In the lungs, a broad range of cell types, including lung epithelial cells, fibroblasts, endothelial cells, tumor cells, stem cells, and various immune cells, can release EVs. In previous reports, EVs derived from lung epithelial cells, endothelial cells, or alveolar macrophages
Emerging functions of EVs in stressed airway physiology
As part of the physiological stress response, exposure to various stimuli can modify EV composition and enhance EV secretion to change the surrounding microenvironment through EV-mediated cell-to-cell communication (Figure 3). EV modification and secretion in stress physiology may be a protective process to eliminate harmful components during adverse conditions such as infection, DNA damage, and smoke exposure 31, 32, 33. For example, Anand et al. investigated the inflammatory functions of
The role of EVs in COPD pathogenesis
Inflammatory airway diseases are airway disorders that are largely related to the presence of persistent inflammation. These related diseases include COPD, pulmonary fibrosis, cystic fibrosis, sarcoidosis, and bronchial asthma, and these diseases are influenced by a combination of environmental, genetic, and epigenetic components [54]. In 2010, Qazi et al. reported that exosomes contribute to the initiation and progression of inflammation in sarcoidosis [55]. To date, some evidence has
The role of EVs in lung cancer pathogenesis
Lung cancer represents an important cause of mortality worldwide. Approximately 85% of all lung cancers are categorized as non-small cell lung cancer (NSCLC). Many therapeutic strategies, including surgery, radiation, chemotherapy, and targeted molecular therapy, are commonly used to treat lung cancer, either alone or in combination. Despite the development of novel molecular therapies [67], the prognosis for lung cancer is still poor, owing primarily to therapeutic resistance and high
Therapeutic roles of mesenchymal stem cell-derived EVs in lung diseases
One major area of interest in EV research is the great potential of various EV functions in therapeutic applications. Currently, stem cell-derived EVs have emerged as a potential solution for tissue repair and wound healing. Some of the most promising stem cell-derived EVs investigated for therapeutic applications in lung tissue regeneration come from mesenchymal stem cells (MSCs).
MSCs can be isolated from adult connective tissues such as bone marrow, umbilical cord, and adipose tissue [92].
Concluding remarks and future perspectives
The involvement of EVs in lung biology has been of great interest over the past few years. In the airway and lung microenvironment, EVs appear to play a key role in intercellular communication under healthy homeostatic regulation conditions as well as in a variety of lung pathologies. EVs derived from a broad range of respiratory cell types micromanage immune responses and disease pathogeneses. Noncancerous cell-derived EVs in the airway demonstrate protective functions against injuries, such
Acknowledgments
This work was supported in part by a Grant-in-Aid for the Third-Term Comprehensive 10 Year Strategy for Cancer Control of Japan, including Awardee of Research Resident Fellowship from the Foundation for Promotion of Cancer Research (Japan); a Grant-in-Aid for scientific research on priority areas in cancer from the Ministry of Education, Culture, Sports, Science and Technology; the Japan Society for the Promotion of Science through the Funding Program for World-Leading Innovative R&D on Science
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2023, Toxicology LettersCitation Excerpt :More research needs to undergo if the assumption wants to be confirmed. Exosomes were able to protect their component well and transport it to target cells or organs over long distances, because of their lipid bilayer membrane structure (Fujita et al., 2015; Tkach and Thery, 2016). The ability of long-distance transport makes it possible to reflect the lesions of target organs by detecting certain specific biomolecules of exosomes in peripheral blood (Kourembanas, 2015; Lu et al., 2019; Zhang et al., 2020a).
Prediction of COPD acute exacerbation in response to air pollution using exosomal circRNA profile and Machine learning
2022, Environment InternationalCitation Excerpt :PRDX2 and ELANE showed increased plasma levels with PM2.5 exposure, which were correlated with the levels of hsa_circ_0005045 (Fig. 2I and J). Because pulmonary epithelial cell-derived exosomes are a significant focus in pulmonary exosome biology (Fujita et al., 2015), we further confirmed that expression levels of hsa_circ_0005045 were upregulated in both bronchial and alveolar epithelial cell-derived exosomes after PM2.5 exposure in vitro. ( Figure S2).
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