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MicroRNA mimicry blocks pulmonary fibrosis
Over the last decade, great enthusiasm has evolved for microRNA (miRNA) therapeutics. Part of the excitement stems from the fact that a miRNA often regulates numerous related mRNAs. As such, modulation of a single miRNA allows for parallel regulation of multiple genes involved in a particular diseas...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287936/ https://www.ncbi.nlm.nih.gov/pubmed/25239947 http://dx.doi.org/10.15252/emmm.201303604 |
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author | Montgomery, Rusty L Yu, Guoying Latimer, Paul A Stack, Christianna Robinson, Kathryn Dalby, Christina M Kaminski, Naftali van Rooij, Eva |
author_facet | Montgomery, Rusty L Yu, Guoying Latimer, Paul A Stack, Christianna Robinson, Kathryn Dalby, Christina M Kaminski, Naftali van Rooij, Eva |
author_sort | Montgomery, Rusty L |
collection | PubMed |
description | Over the last decade, great enthusiasm has evolved for microRNA (miRNA) therapeutics. Part of the excitement stems from the fact that a miRNA often regulates numerous related mRNAs. As such, modulation of a single miRNA allows for parallel regulation of multiple genes involved in a particular disease. While many studies have shown therapeutic efficacy using miRNA inhibitors, efforts to restore or increase the function of a miRNA have been lagging behind. The miR-29 family has gained a lot of attention for its clear function in tissue fibrosis. This fibroblast-enriched miRNA family is downregulated in fibrotic diseases which induces a coordinate increase of many extracellular matrix genes. Here, we show that intravenous injection of synthetic RNA duplexes can increase miR-29 levels in vivo for several days. Moreover, therapeutic delivery of these miR-29 mimics during bleomycin-induced pulmonary fibrosis restores endogenous miR-29 function whereby decreasing collagen expression and blocking and reversing pulmonary fibrosis. Our data support the feasibility of using miRNA mimics to therapeutically increase miRNAs and indicate miR-29 to be a potent therapeutic miRNA for treating pulmonary fibrosis. |
format | Online Article Text |
id | pubmed-4287936 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-42879362015-01-12 MicroRNA mimicry blocks pulmonary fibrosis Montgomery, Rusty L Yu, Guoying Latimer, Paul A Stack, Christianna Robinson, Kathryn Dalby, Christina M Kaminski, Naftali van Rooij, Eva EMBO Mol Med Report Over the last decade, great enthusiasm has evolved for microRNA (miRNA) therapeutics. Part of the excitement stems from the fact that a miRNA often regulates numerous related mRNAs. As such, modulation of a single miRNA allows for parallel regulation of multiple genes involved in a particular disease. While many studies have shown therapeutic efficacy using miRNA inhibitors, efforts to restore or increase the function of a miRNA have been lagging behind. The miR-29 family has gained a lot of attention for its clear function in tissue fibrosis. This fibroblast-enriched miRNA family is downregulated in fibrotic diseases which induces a coordinate increase of many extracellular matrix genes. Here, we show that intravenous injection of synthetic RNA duplexes can increase miR-29 levels in vivo for several days. Moreover, therapeutic delivery of these miR-29 mimics during bleomycin-induced pulmonary fibrosis restores endogenous miR-29 function whereby decreasing collagen expression and blocking and reversing pulmonary fibrosis. Our data support the feasibility of using miRNA mimics to therapeutically increase miRNAs and indicate miR-29 to be a potent therapeutic miRNA for treating pulmonary fibrosis. BlackWell Publishing Ltd 2014-10 2014-09-19 /pmc/articles/PMC4287936/ /pubmed/25239947 http://dx.doi.org/10.15252/emmm.201303604 Text en © 2014 miRagen Therapeutics. Published under the terms of the CC BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Report Montgomery, Rusty L Yu, Guoying Latimer, Paul A Stack, Christianna Robinson, Kathryn Dalby, Christina M Kaminski, Naftali van Rooij, Eva MicroRNA mimicry blocks pulmonary fibrosis |
title | MicroRNA mimicry blocks pulmonary fibrosis |
title_full | MicroRNA mimicry blocks pulmonary fibrosis |
title_fullStr | MicroRNA mimicry blocks pulmonary fibrosis |
title_full_unstemmed | MicroRNA mimicry blocks pulmonary fibrosis |
title_short | MicroRNA mimicry blocks pulmonary fibrosis |
title_sort | microrna mimicry blocks pulmonary fibrosis |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287936/ https://www.ncbi.nlm.nih.gov/pubmed/25239947 http://dx.doi.org/10.15252/emmm.201303604 |
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