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Pulmonary microRNA profiling: implications in upper lobe predominant lung disease

BACKGROUND: Numerous pulmonary diseases manifest with upper lobe predominance including cystic fibrosis, smoking-related chronic obstructive pulmonary disease, and tuberculosis. Zonal hypoxia, characteristic of these pulmonary maladies, and oxygen stress in general is known to exert profound effects...

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Autores principales: Armstrong, David A., Nymon, Amanda B., Ringelberg, Carol S., Lesseur, Corina, Hazlett, Haley F., Howard, Louisa, Marsit, Carmen J., Ashare, Alix
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450072/
https://www.ncbi.nlm.nih.gov/pubmed/28572860
http://dx.doi.org/10.1186/s13148-017-0355-1
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author Armstrong, David A.
Nymon, Amanda B.
Ringelberg, Carol S.
Lesseur, Corina
Hazlett, Haley F.
Howard, Louisa
Marsit, Carmen J.
Ashare, Alix
author_facet Armstrong, David A.
Nymon, Amanda B.
Ringelberg, Carol S.
Lesseur, Corina
Hazlett, Haley F.
Howard, Louisa
Marsit, Carmen J.
Ashare, Alix
author_sort Armstrong, David A.
collection PubMed
description BACKGROUND: Numerous pulmonary diseases manifest with upper lobe predominance including cystic fibrosis, smoking-related chronic obstructive pulmonary disease, and tuberculosis. Zonal hypoxia, characteristic of these pulmonary maladies, and oxygen stress in general is known to exert profound effects on various important aspects of cell biology. Lung macrophages are major participants in the pulmonary innate immune response and regional differences in macrophage responsiveness to hypoxia may contribute in the development of lung disease. MicroRNAs are ubiquitous regulators of human biology and emerging evidence indicates altered microRNA expression modulates respiratory disease processes. The objective of this study is to gain insight into the epigenetic and cellular mechanisms influencing regional differences in lung disease by investigating effect of hypoxia on regional microRNA expression in the lung. All studies were performed using primary alveolar macrophages (n = 10) or bronchoalveolar lavage fluid (n = 16) isolated from human subjects. MicroRNA was assayed via the NanoString nCounter microRNA assay. RESULTS: Divergent molecular patterns of microRNA expression were observed in alternate lung lobes, specifically noted was disparate expression of miR-93 and miR-4454 in alveolar macrophages along with altered expression of miR-451a and miR-663a in bronchoalveolar lavage fluid. Gene ontology was used to identify potential downstream targets of divergent microRNAs. Targets include cytokines and matrix metalloproteinases, molecules that could have a significant impact on pulmonary inflammation and fibrosis. CONCLUSIONS: Our findings show variant regional microRNA expression associated with hypoxia in alveolar macrophages and BAL fluid in the lung—upper vs lower lobe. Future studies should address whether these specific microRNAs may act intracellularly, in a paracrine/endocrine manner to direct the innate immune response or may ultimately be involved in pulmonary host-to-pathogen trans-kingdom cross-talk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-017-0355-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-54500722017-06-01 Pulmonary microRNA profiling: implications in upper lobe predominant lung disease Armstrong, David A. Nymon, Amanda B. Ringelberg, Carol S. Lesseur, Corina Hazlett, Haley F. Howard, Louisa Marsit, Carmen J. Ashare, Alix Clin Epigenetics Research BACKGROUND: Numerous pulmonary diseases manifest with upper lobe predominance including cystic fibrosis, smoking-related chronic obstructive pulmonary disease, and tuberculosis. Zonal hypoxia, characteristic of these pulmonary maladies, and oxygen stress in general is known to exert profound effects on various important aspects of cell biology. Lung macrophages are major participants in the pulmonary innate immune response and regional differences in macrophage responsiveness to hypoxia may contribute in the development of lung disease. MicroRNAs are ubiquitous regulators of human biology and emerging evidence indicates altered microRNA expression modulates respiratory disease processes. The objective of this study is to gain insight into the epigenetic and cellular mechanisms influencing regional differences in lung disease by investigating effect of hypoxia on regional microRNA expression in the lung. All studies were performed using primary alveolar macrophages (n = 10) or bronchoalveolar lavage fluid (n = 16) isolated from human subjects. MicroRNA was assayed via the NanoString nCounter microRNA assay. RESULTS: Divergent molecular patterns of microRNA expression were observed in alternate lung lobes, specifically noted was disparate expression of miR-93 and miR-4454 in alveolar macrophages along with altered expression of miR-451a and miR-663a in bronchoalveolar lavage fluid. Gene ontology was used to identify potential downstream targets of divergent microRNAs. Targets include cytokines and matrix metalloproteinases, molecules that could have a significant impact on pulmonary inflammation and fibrosis. CONCLUSIONS: Our findings show variant regional microRNA expression associated with hypoxia in alveolar macrophages and BAL fluid in the lung—upper vs lower lobe. Future studies should address whether these specific microRNAs may act intracellularly, in a paracrine/endocrine manner to direct the innate immune response or may ultimately be involved in pulmonary host-to-pathogen trans-kingdom cross-talk. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13148-017-0355-1) contains supplementary material, which is available to authorized users. BioMed Central 2017-05-30 /pmc/articles/PMC5450072/ /pubmed/28572860 http://dx.doi.org/10.1186/s13148-017-0355-1 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Armstrong, David A.
Nymon, Amanda B.
Ringelberg, Carol S.
Lesseur, Corina
Hazlett, Haley F.
Howard, Louisa
Marsit, Carmen J.
Ashare, Alix
Pulmonary microRNA profiling: implications in upper lobe predominant lung disease
title Pulmonary microRNA profiling: implications in upper lobe predominant lung disease
title_full Pulmonary microRNA profiling: implications in upper lobe predominant lung disease
title_fullStr Pulmonary microRNA profiling: implications in upper lobe predominant lung disease
title_full_unstemmed Pulmonary microRNA profiling: implications in upper lobe predominant lung disease
title_short Pulmonary microRNA profiling: implications in upper lobe predominant lung disease
title_sort pulmonary microrna profiling: implications in upper lobe predominant lung disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5450072/
https://www.ncbi.nlm.nih.gov/pubmed/28572860
http://dx.doi.org/10.1186/s13148-017-0355-1
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