Abstract
MicroRNAs are known to regulate important pathways in asthma pathology including the IL-6 and IFN pathways. MicroRNAs have been found not only within cells but also within extracellular vesicles such as exosomes. In this study, we particularly focused on microRNA cargo of nanovesicles in bronchoalveolar lavage of severe asthmatic patients. We extracted nanovesicle RNA using a serial filtration method. RNA content was analyzed with small RNA sequencing and mapped to pathways affected using WebGestalt 2017 Software. We report that severe asthma patients have deficient loading of microRNAs into their airway luminal nanovesicles and an altered profile of small RNA nanovesicle content (i.e., ribosomal RNA and broken transcripts, etc.). This decrease in microRNA cargo is predicted to increase the expression of genes by promoting inflammation and remodeling. Consistently, a network of microRNAs was associated with decreased FEV1 and increased eosinophilic and neutrophilic inflammation in severe asthma. MicroRNAs in airway nanovesicles may, thus, be valid biomarkers to define abnormal biological disease processes in severe asthma and monitor the impact of interventional therapies.
Highlights
Exosomes are extracellular membrane-derived vesicles, of approximately 30–150 nm in diameter, which are generated and released in a tightly regulated manner [1]
We have described that microRNAs can affect important pathways (IL-6 and Interferon production) in airway cells from asthmatic patients [3,4]
MiR-155 and miR-27a were used as positive controls of the presence of microRNAs since they are relatively abundant in airway cells [3,4]
Summary
Exosomes are extracellular membrane-derived vesicles, of approximately 30–150 nm in diameter, which are generated and released in a tightly regulated manner [1]. They may contain DNA, proteins, lipids, and RNA molecules, including microRNAs, and participate in intercellular communication. Exosomal microRNAs have been evaluated in exhaled breath, bronchoalveolar lavage, and sputum supernatant samples [5,6,7]. The exosomal microRNA cargo in bronchoalveolar lavage fluid (BALF) is dysregulated in mild asthma [6]. No assessments have been undertaken of BALF exosomal microRNA profiles in severe asthma, which is a disease that is only partially responsive to treatment and is recognized to be associated with epithelial dysfunction and altered luminal inflammation [8]
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