MicroRNA expression is altered in an ovalbumin-induced asthma model and targeting miR-155 with antagomirs reveals cellular specificity

Plank, MW; Maltby, S; Tay, HL; Stewart, J; Eyers, F; Hansbro, PM; Foster, PS

MicroRNA expression is altered in an ovalbumin-induced asthma model and targeting miR-155 with antagomirs reveals cellular specificity

Plank, MW Maltby, S Tay, HL Stewart, J Eyers, F Hansbro, PM

Foster, PS

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Publication Type:: Journal Article
Citation:: PLoS ONE, 2015, 10 (12)
Issue Date:: 2015-12-01

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Field	Value	Language
dc.contributor.author	Plank, MW	en_US
dc.contributor.author	Maltby, S	en_US
dc.contributor.author	Tay, HL	en_US
dc.contributor.author	Stewart, J	en_US
dc.contributor.author	Eyers, F	en_US
dc.contributor.author	Hansbro, PM https://orcid.org/0000-0002-4741-3035	en_US
dc.contributor.author	Foster, PS	en_US
dc.date.available	2015-11-24	en_US
dc.date.issued	2015-12-01	en_US
dc.identifier.citation	PLoS ONE, 2015, 10 (12)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/128823
dc.description.abstract	©2015 Plank et al. 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 arecredited. 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.	en_US
dc.relation.ispartof	PLoS ONE	en_US
dc.relation.isbasedon	10.1371/journal.pone.0144810	en_US
dc.subject.classification	General Science & Technology	en_US
dc.subject.mesh	Lung	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Asthma	en_US
dc.subject.mesh	Disease Models, Animal	en_US
dc.subject.mesh	Dexamethasone	en_US
dc.subject.mesh	Ovalbumin	en_US
dc.subject.mesh	MicroRNAs	en_US
dc.subject.mesh	Oligonucleotides	en_US
dc.subject.mesh	Gene Expression Profiling	en_US
dc.subject.mesh	Organ Specificity	en_US
dc.subject.mesh	Gene Expression Regulation	en_US
dc.title	MicroRNA expression is altered in an ovalbumin-induced asthma model and targeting miR-155 with antagomirs reveals cellular specificity	en_US
dc.type	Journal Article
utslib.citation.volume	12	en_US
utslib.citation.volume	10	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	12	en_US
pubs.publication-status	Published	en_US
pubs.volume	10	en_US

Abstract:

©2015 Plank et al. 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 arecredited. 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/128823