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Small RNA Species and microRNA Profiles are Altered in Severe Asthma Nanovesicles from Broncho Alveolar Lavage and Associate with Impaired Lung Function and Inflammation

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Clinical and Experimental Sciences, Sir Henry Wellcome Laboratories, University of Southampton School of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK
2
NIHR Southampton Respiratory Biomedical Research Unit, Southampton Centre for Biomedical Research MP812, Southampton General Hospital, Southampton SO16 6YD, UK
*
Authors to whom correspondence should be addressed.
Non-Coding RNA 2019, 5(4), 51; https://doi.org/10.3390/ncrna5040051
Received: 30 September 2019 / Revised: 24 October 2019 / Accepted: 30 October 2019 / Published: 2 November 2019
(This article belongs to the Special Issue Non-Coding RNA and the Immune System)
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. View Full-Text
Keywords: microRNAs; severe asthma; exosomes; lung function; FEV1; eosinophils; neutrophils microRNAs; severe asthma; exosomes; lung function; FEV1; eosinophils; neutrophils
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Francisco-Garcia, A.S.; Garrido-Martín, E.M.; Rupani, H.; Lau, L.C.K.; Martinez-Nunez, R.T.; Howarth, P.H.; Sanchez-Elsner, T. Small RNA Species and microRNA Profiles are Altered in Severe Asthma Nanovesicles from Broncho Alveolar Lavage and Associate with Impaired Lung Function and Inflammation. Non-Coding RNA 2019, 5, 51.

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