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EMBO Mol Med. 2014 Oct;6(10):1347-56. doi: 10.15252/emmm.201303604.

MicroRNA mimicry blocks pulmonary fibrosis.

Author information

1
miRagen Therapeutics, Inc, Boulder, CO, USA.
2
Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
3
Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA naftali.kaminski@yale.edu e.vanrooij@hubrecht.eu.
4
miRagen Therapeutics, Inc, Boulder, CO, USA Hubrecht Institute, KNAW and University Medical Center Utrecht, Utrecht, The Netherlands naftali.kaminski@yale.edu e.vanrooij@hubrecht.eu.

Abstract

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.

KEYWORDS:

miR‐29; microRNA; mimic; pulmonary fibrosis; therapeutics

PMID:
25239947
PMCID:
PMC4287936
DOI:
10.15252/emmm.201303604
[Indexed for MEDLINE]
Free PMC Article

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