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Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle
BACKGROUND: The mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary airway smooth muscle cells (ASMCs), whereas chang...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Mosby
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338875/ https://www.ncbi.nlm.nih.gov/pubmed/27484035 http://dx.doi.org/10.1016/j.jaci.2016.06.014 |
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author | Austin, Philip J. Tsitsiou, Eleni Boardman, Charlotte Jones, Simon W. Lindsay, Mark A. Adcock, Ian M. Chung, Kian Fan Perry, Mark M. |
author_facet | Austin, Philip J. Tsitsiou, Eleni Boardman, Charlotte Jones, Simon W. Lindsay, Mark A. Adcock, Ian M. Chung, Kian Fan Perry, Mark M. |
author_sort | Austin, Philip J. |
collection | PubMed |
description | BACKGROUND: The mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary airway smooth muscle cells (ASMCs), whereas changed expression has been observed in CD8 T cells from patients with severe asthma. METHODS: Primary ASMCs were isolated from healthy subjects (n = 9) and patients classified as having nonsevere (n = 9) or severe (n = 9) asthma. ASMCs were exposed to dexamethasone and FCS. mRNA and lncRNA expression was measured by using a microarray and quantitative real-time PCR. Bioinformatic analysis was used to examine relevant biological pathways. Finally, the lncRNA plasmacytoma variant translocation 1 (PVT1) was inhibited by transfection of primary ASMCs with small interfering RNAs, and the effect on ASMC phenotype was examined. RESULTS: The mRNA expression profile was significantly different between patient groups after exposure to dexamethasone and FCS, and these were associated with biological pathways that might be relevant to the pathogenesis of asthma, including cellular proliferation and pathways associated with glucocorticoid activity. We also observed a significant change in lncRNA expression, yet the expression of only one lncRNA (PVT1) is decreased in patients with corticosteroid-sensitive nonsevere asthma and increased in patients with corticosteroid-insensitive severe asthma. Subsequent targeting studies demonstrated the importance of this lncRNA in controlling both proliferation and IL-6 release in ASMCs from patients with severe asthma. CONCLUSIONS: lncRNAs are associated with the aberrant phenotype observed in ASMCs from asthmatic patients. Targeting PVT1 might be effective in reducing airway remodeling in asthmatic patients. |
format | Online Article Text |
id | pubmed-5338875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Mosby |
record_format | MEDLINE/PubMed |
spelling | pubmed-53388752017-03-13 Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle Austin, Philip J. Tsitsiou, Eleni Boardman, Charlotte Jones, Simon W. Lindsay, Mark A. Adcock, Ian M. Chung, Kian Fan Perry, Mark M. J Allergy Clin Immunol Asthma and Lower Airway Disease BACKGROUND: The mechanism underlying nonsevere and severe asthma remains unclear, although it is commonly associated with increased airway smooth muscle (ASM) mass. Long noncoding RNAs (lncRNAs) are known to be important in regulating healthy primary airway smooth muscle cells (ASMCs), whereas changed expression has been observed in CD8 T cells from patients with severe asthma. METHODS: Primary ASMCs were isolated from healthy subjects (n = 9) and patients classified as having nonsevere (n = 9) or severe (n = 9) asthma. ASMCs were exposed to dexamethasone and FCS. mRNA and lncRNA expression was measured by using a microarray and quantitative real-time PCR. Bioinformatic analysis was used to examine relevant biological pathways. Finally, the lncRNA plasmacytoma variant translocation 1 (PVT1) was inhibited by transfection of primary ASMCs with small interfering RNAs, and the effect on ASMC phenotype was examined. RESULTS: The mRNA expression profile was significantly different between patient groups after exposure to dexamethasone and FCS, and these were associated with biological pathways that might be relevant to the pathogenesis of asthma, including cellular proliferation and pathways associated with glucocorticoid activity. We also observed a significant change in lncRNA expression, yet the expression of only one lncRNA (PVT1) is decreased in patients with corticosteroid-sensitive nonsevere asthma and increased in patients with corticosteroid-insensitive severe asthma. Subsequent targeting studies demonstrated the importance of this lncRNA in controlling both proliferation and IL-6 release in ASMCs from patients with severe asthma. CONCLUSIONS: lncRNAs are associated with the aberrant phenotype observed in ASMCs from asthmatic patients. Targeting PVT1 might be effective in reducing airway remodeling in asthmatic patients. Mosby 2017-03 /pmc/articles/PMC5338875/ /pubmed/27484035 http://dx.doi.org/10.1016/j.jaci.2016.06.014 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Asthma and Lower Airway Disease Austin, Philip J. Tsitsiou, Eleni Boardman, Charlotte Jones, Simon W. Lindsay, Mark A. Adcock, Ian M. Chung, Kian Fan Perry, Mark M. Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle |
title | Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle |
title_full | Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle |
title_fullStr | Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle |
title_full_unstemmed | Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle |
title_short | Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle |
title_sort | transcriptional profiling identifies the long noncoding rna plasmacytoma variant translocation (pvt1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle |
topic | Asthma and Lower Airway Disease |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5338875/ https://www.ncbi.nlm.nih.gov/pubmed/27484035 http://dx.doi.org/10.1016/j.jaci.2016.06.014 |
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