MicroRNA mimicry blocks pulmonary fibrosis

Rusty L Montgomery, Guoying Yu, Paul A Latimer, Christianna Stack, Kathryn Robinson, Christina M Dalby, Naftali Kaminski, Eva van Rooij

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)1347-56
Number of pages10
JournalEMBO Molecular Medicine
Volume6
Issue number10
DOIs
Publication statusPublished - Oct 2014

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