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MicroRNA Expression Is Altered in an Ovalbumin-Induced Asthma Model and Targeting miR-155 with Antagomirs Reveals Cellular Specificity

MicroRNAs are post-transcriptional regulators of gene expression that are differentially regulated during development and in inflammatory diseases. A role for miRNAs in allergic asthma is emerging and further investigation is required to determine whether they may serve as potential therapeutic targ...

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Autores principales: Plank, Maximilian W., Maltby, Steven, Tay, Hock L., Stewart, Jessica, Eyers, Fiona, Hansbro, Philip M., Foster, Paul S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691205/
https://www.ncbi.nlm.nih.gov/pubmed/26693910
http://dx.doi.org/10.1371/journal.pone.0144810
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author Plank, Maximilian W.
Maltby, Steven
Tay, Hock L.
Stewart, Jessica
Eyers, Fiona
Hansbro, Philip M.
Foster, Paul S.
author_facet Plank, Maximilian W.
Maltby, Steven
Tay, Hock L.
Stewart, Jessica
Eyers, Fiona
Hansbro, Philip M.
Foster, Paul S.
author_sort Plank, Maximilian W.
collection PubMed
description MicroRNAs are post-transcriptional regulators of gene expression that are differentially regulated during development and in inflammatory diseases. A role for miRNAs in allergic asthma is emerging and further investigation is required to determine whether they may serve as potential therapeutic targets. We profiled miRNA expression in murine lungs from an ovalbumin-induced allergic airways disease model, and compared expression to animals receiving dexamethasone treatment and non-allergic controls. Our analysis identified 29 miRNAs that were significantly altered during allergic inflammation. Target prediction analysis revealed novel genes with altered expression in allergic airways disease and suggests synergistic miRNA regulation of target mRNAs. To assess the impacts of one induced miRNA on pathology, we targeted miR-155-5p using a specific antagomir. Antagomir administration successfully reduced miR-155-5p expression with high specificity, but failed to alter the disease phenotype. Interestingly, further investigation revealed that antagomir delivery has variable efficacy across different immune cell types, effectively targeting myeloid cell populations, but exhibiting poor uptake in lymphocytes. Our findings demonstrate that antagomir-based targeting of miRNA function in the lung is highly specific, but highlights cell-specificity as a key limitation to be considered for antagomir-based strategies as therapeutics.
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spelling pubmed-46912052015-12-31 MicroRNA Expression Is Altered in an Ovalbumin-Induced Asthma Model and Targeting miR-155 with Antagomirs Reveals Cellular Specificity Plank, Maximilian W. Maltby, Steven Tay, Hock L. Stewart, Jessica Eyers, Fiona Hansbro, Philip M. Foster, Paul S. PLoS One Research Article MicroRNAs are post-transcriptional regulators of gene expression that are differentially regulated during development and in inflammatory diseases. A role for miRNAs in allergic asthma is emerging and further investigation is required to determine whether they may serve as potential therapeutic targets. We profiled miRNA expression in murine lungs from an ovalbumin-induced allergic airways disease model, and compared expression to animals receiving dexamethasone treatment and non-allergic controls. Our analysis identified 29 miRNAs that were significantly altered during allergic inflammation. Target prediction analysis revealed novel genes with altered expression in allergic airways disease and suggests synergistic miRNA regulation of target mRNAs. To assess the impacts of one induced miRNA on pathology, we targeted miR-155-5p using a specific antagomir. Antagomir administration successfully reduced miR-155-5p expression with high specificity, but failed to alter the disease phenotype. Interestingly, further investigation revealed that antagomir delivery has variable efficacy across different immune cell types, effectively targeting myeloid cell populations, but exhibiting poor uptake in lymphocytes. Our findings demonstrate that antagomir-based targeting of miRNA function in the lung is highly specific, but highlights cell-specificity as a key limitation to be considered for antagomir-based strategies as therapeutics. Public Library of Science 2015-12-22 /pmc/articles/PMC4691205/ /pubmed/26693910 http://dx.doi.org/10.1371/journal.pone.0144810 Text en © 2015 Plank et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Plank, Maximilian W.
Maltby, Steven
Tay, Hock L.
Stewart, Jessica
Eyers, Fiona
Hansbro, Philip M.
Foster, Paul S.
MicroRNA Expression Is Altered in an Ovalbumin-Induced Asthma Model and Targeting miR-155 with Antagomirs Reveals Cellular Specificity
title MicroRNA Expression Is Altered in an Ovalbumin-Induced Asthma Model and Targeting miR-155 with Antagomirs Reveals Cellular Specificity
title_full MicroRNA Expression Is Altered in an Ovalbumin-Induced Asthma Model and Targeting miR-155 with Antagomirs Reveals Cellular Specificity
title_fullStr MicroRNA Expression Is Altered in an Ovalbumin-Induced Asthma Model and Targeting miR-155 with Antagomirs Reveals Cellular Specificity
title_full_unstemmed MicroRNA Expression Is Altered in an Ovalbumin-Induced Asthma Model and Targeting miR-155 with Antagomirs Reveals Cellular Specificity
title_short MicroRNA Expression Is Altered in an Ovalbumin-Induced Asthma Model and Targeting miR-155 with Antagomirs Reveals Cellular Specificity
title_sort microrna expression is altered in an ovalbumin-induced asthma model and targeting mir-155 with antagomirs reveals cellular specificity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4691205/
https://www.ncbi.nlm.nih.gov/pubmed/26693910
http://dx.doi.org/10.1371/journal.pone.0144810
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