Altered microRNA profiles in bronchoalveolar lavage fluid exosomes in asthmatic patients
01 Mar 2013-The Journal of Allergy and Clinical Immunology (J Allergy Clin Immunol)-Vol. 131, Iss: 3, pp 894-903
TL;DR: Substantial differences in exosomal miRNA profiles between healthy subjects and patients with unprovoked, mild, stable asthma are demonstrated, which might be important in the inflammatory response leading to bronchial hyperresponsiveness and asthma.
Abstract: Background Asthma is characterized by increased airway narrowing in response to nonspecific stimuli. The disorder is influenced by both environmental and genetic factors. Exosomes are nanosized vesicles of endosomal origin released from inflammatory and epithelial cells that have been implicated in asthma. In this study we characterized the microRNA (miRNA) content of exosomes in healthy control subjects and patients with mild intermittent asthma both at unprovoked baseline and in response to environmental challenge. Objective To investigate alterations in bronchoalveolar lavage fluid (BALF) exosomal miRNA profiles due to asthma, and following subway air exposure. Methods Exosomes were isolated from BALF from healthy control subjects (n = 10) and patients with mild intermittent asthma (n = 10) after subway and control exposures. Exosomal RNA was analyzed by using microarrays containing probes for 894 human miRNAs, and selected findings were validated with quantitative RT-PCR. Results were analyzed by using multivariate modeling. Results The presence of miRNAs was confirmed in exosomes from BALF of both asthmatic patients and healthy control subjects. Significant differences in BALF exosomal miRNA was detected for 24 miRNAs with a subset of 16 miRNAs, including members of the let-7 and miRNA-200 families, providing robust classification of patients with mild nonsymptomatic asthma from healthy subjects with 72% cross-validated predictive power (Q 2 = 0.72). In contrast, subway exposure did not cause any significant alterations in miRNA profiles. Conclusion These studies demonstrate substantial differences in exosomal miRNA profiles between healthy subjects and patients with unprovoked, mild, stable asthma. These changes might be important in the inflammatory response leading to bronchial hyperresponsiveness and asthma.
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University of Helsinki1, Semmelweis University2, Hungarian Academy of Sciences3, University of Szeged4, University of Palermo5, University of Porto6, Institute of Molecular Pathology and Immunology of the University of Porto7, Autonomous University of Barcelona8, Instituto de Biologia Molecular e Celular9, Ikerbasque10, Harvard University11, University of Duisburg-Essen12, Salk Institute for Biological Studies13, Paracelsus Private Medical University of Salzburg14, University of Colorado Denver15, Bilkent University16, Middle East Technical University17, University of Southern Denmark18, Statens Serum Institut19, Ghent University Hospital20, Oslo University Hospital21, University of Belgrade22, University of Ljubljana23, University of Mainz24, Finnish Red Cross25, University of Gothenburg26, Latvian Biomedical Research and Study centre27, University of Applied Sciences and Arts Northwestern Switzerland FHNW28, University of Valencia29, Centro Nacional de Investigaciones Cardiovasculares30, University of Freiburg31, Utrecht University32, Trinity College, Dublin33, University of Barcelona34, Catalan Institution for Research and Advanced Studies35, International University Of Catalonia36, Aarhus University Hospital37
TL;DR: A comprehensive overview of the current understanding of the physiological roles of EVs is provided, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia.
Abstract: In the past decade, extracellular vesicles (EVs) have been recognized as potent vehicles of intercellular communication, both in prokaryotes and eukaryotes. This is due to their capacity to transfer proteins, lipids and nucleic acids, thereby influencing various physiological and pathological functions of both recipient and parent cells. While intensive investigation has targeted the role of EVs in different pathological processes, for example, in cancer and autoimmune diseases, the EV-mediated maintenance of homeostasis and the regulation of physiological functions have remained less explored. Here, we provide a comprehensive overview of the current understanding of the physiological roles of EVs, which has been written by crowd-sourcing, drawing on the unique EV expertise of academia-based scientists, clinicians and industry based in 27 European countries, the United States and Australia. This review is intended to be of relevance to both researchers already working on EV biology and to newcomers who will encounter this universal cell biological system. Therefore, here we address the molecular contents and functions of EVs in various tissues and body fluids from cell systems to organs. We also review the physiological mechanisms of EVs in bacteria, lower eukaryotes and plants to highlight the functional uniformity of this emerging communication system.
3,690 citations
Cites background from "Altered microRNA profiles in bronch..."
...The presence of RNA and miRNA in those EVs has also been documented (286)....
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01 Jan 2000
3,536 citations
TL;DR: The need for standardization of specimen handling, appropriate normative controls, and isolation and analysis techniques to facilitate comparison of results is emphasized, and it is recognized that continual development and evaluation of techniques will be necessary as new knowledge is amassed.
Abstract: The emergence of publications on extracellular RNA (exRNA) and extracellular vesicles (EV) has highlighted the potential of these molecules and vehicles as biomarkers of disease and therapeutic targets. These findings have created a paradigm shift, most prominently in the field of oncology, prompting expanded interest in the field and dedication of funds for EV research. At the same time, understanding of EV subtypes, biogenesis, cargo and mechanisms of shuttling remains incomplete. The techniques that can be harnessed to address the many gaps in our current knowledge were the subject of a special workshop of the International Society for Extracellular Vesicles (ISEV) in New York City in October 2012. As part of the “ISEV Research Seminar: Analysis and Function of RNA in Extracellular Vesicles (evRNA)”, 6 round-table discussions were held to provide an evidence-based framework for isolation and analysis of EV, purification and analysis of associated RNA molecules, and molecular engineering of EV for therapeutic intervention. This article arises from the discussion of EV isolation and analysis at that meeting. The conclusions of the round table are supplemented with a review of published materials and our experience. Controversies and outstanding questions are identified that may inform future research and funding priorities. While we emphasize the need for standardization of specimen handling, appropriate normative controls, and isolation and analysis techniques to facilitate comparison of results, we also recognize that continual development and evaluation of techniques will be necessary as new knowledge is amassed. On many points, consensus has not yet been achieved and must be built through the reporting of well-controlled experiments. Keywords: extracellular vesicle; exosome; microvesicle; standardization; isolation (Published: 27 May 2013) Citation: Journal of Extracellular Vesicles 2013, 2 : 20360 - http://dx.doi.org/10.3402/jev.v2i0.20360
1,840 citations
TL;DR: The current understanding of physiological and pathophysiological roles of exosomes, their potential applications as diagnostic markers, and current efforts to develop improved exosome‐based drug delivery systems are reviewed.
690 citations
Cites background from "Altered microRNA profiles in bronch..."
...2013), kidney (Spanu, van Roeyen, Denecke, Floege, & Muhlfeld, 2014), lung (Levanen et al., 2013), and arteries (Hoefer et al....
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...…as biological indicators for a number of non-cancer diseases of multiple organs including the CNS (Kawikova & Askenase, 2015), liver (Masyuk, Masyuk, & Larusso, 2013), kidney (Spanu, van Roeyen, Denecke, Floege, & Muhlfeld, 2014), lung (Levanen et al., 2013), and arteries (Hoefer et al., 2015)....
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...With respect to lung disease, exosomes from broncho-alveolar lavage fluids from asthmatic patients or healthy subjects exhibited different miRNA profiles (Levanen et al., 2013)....
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TL;DR: The biogenesis of exosomes, their molecular composition, and their role as messengers of intercellular communication are reviewed, focusing on their potential as therapeutic vectors for stem cell therapy.
Abstract: Mesenchymal stem cells (MSCs), whose mechanism of action is predominantly paracrine, are being widely tested for the treatment of a variety of human diseases. No one factor has been proven sufficient to mediate the therapeutic effects of MSCs. However, exosomes--membrane vesicles secreted by many cells, including MSCs--are appealing candidates as vectors of their efficacy. Exosomes can transport and deliver a large cargo of proteins, lipids, and nucleic acids and can modify cell and organ function. In addition to their key role as vehicles of intercellular communication, exosomes are increasingly recognized as biomarkers and prognosticators of disease. Moreover, they have the potential to be used as vehicles of gene and drug delivery for clinical application. This article reviews the biogenesis of exosomes, their molecular composition, and their role as messengers of intercellular communication, focusing on their potential as therapeutic vectors for stem cell therapy.
540 citations
Cites background from "Altered microRNA profiles in bronch..."
...Exosomes isolated from bronchoalveolar lavage fluid of patients with asthma contain unique miRNA species that differ from those of control patients (94)....
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"Altered microRNA profiles in bronch..." refers methods in this paper
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