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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

Small RNA species and microRNA profiles are altered in severe asthma nanovesicles from broncho alveolar lavage and associate with impaired lung function and inflammation
Small RNA species and microRNA profiles are altered in severe asthma nanovesicles from broncho alveolar lavage and associate with impaired lung function and inflammation
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.
2311-553X
Francisco Garcia, Ana Soraia
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Garrido Martin, Eva
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Rupani, Hitasha
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Lau, Laurie
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Martinez-nunez, Rocio T
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Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Francisco Garcia, Ana Soraia
0d675d21-b92a-4d66-81b6-9f2a82545ade
Garrido Martin, Eva
bba99077-0684-4516-8a15-e80409c12734
Rupani, Hitasha
cbc7068a-4279-4c8e-b83f-353210711062
Lau, Laurie
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Martinez-nunez, Rocio T
a6069f08-55cf-4477-b895-9c4fdd2ee5ee
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d

Francisco Garcia, Ana Soraia, Garrido Martin, Eva, Rupani, Hitasha, Lau, Laurie, Martinez-nunez, Rocio T, Howarth, Peter and Sanchez-Elsner, Tilman (2019) Small RNA species and microRNA profiles are altered in severe asthma nanovesicles from broncho alveolar lavage and associate with impaired lung function and inflammation. Noncoding RNA, 54 (1). (doi:10.3390/ncrna5040051).

Record type: Article

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.

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Accepted/In Press date: 30 October 2019
Published date: 2 November 2019

Identifiers

Local EPrints ID: 441860
URI: http://eprints.soton.ac.uk/id/eprint/441860
ISSN: 2311-553X
PURE UUID: 7953007a-bde2-41dd-91e0-542aa1ad7d57
ORCID for Tilman Sanchez-Elsner: ORCID iD orcid.org/0000-0003-1915-2410

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Date deposited: 30 Jun 2020 16:31
Last modified: 29 Jul 2020 01:37

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