title: MicroRNA mimicry blocks pulmonary fibrosis.
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.
authors.affiliation: miRagen Therapeutics, Inc, Boulder, CO, USA.
authors.forename: Rusty L
authors.initials: RL
authors.lastname: Montgomery
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA.
authors.forename: Guoying
authors.initials: G
authors.lastname: Yu
authors.affiliation: miRagen Therapeutics, Inc, Boulder, CO, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Latimer
authors.affiliation: miRagen Therapeutics, Inc, Boulder, CO, USA.
authors.forename: Christianna
authors.initials: C
authors.lastname: Stack
authors.affiliation: miRagen Therapeutics, Inc, Boulder, CO, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Robinson
authors.affiliation: miRagen Therapeutics, Inc, Boulder, CO, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Dalby
authors.affiliation: Section of Pulmonary, Critical Care and Sleep Medicine, Yale School of Medicine, New Haven, CT, USA naftali.kaminski@yale.edu e.vanrooij@hubrecht.eu.
authors.forename: Naftali
authors.initials: N
authors.lastname: Kaminski
authors.affiliation: 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.
authors.forename: Eva
authors.initials: E
authors.lastname: van Rooij
mesh_terms: D000818:Animals; D001761:Bleomycin; D015152:Blotting, Northern; D002460:Cell Line; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D018716:Molecular Mimicry / Q000235:genetics* / Q000502:physiology; D041681:NIH 3T3 Cells; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D001761:Bleomycin
keywords: miR‐29; microRNA; mimic; pulmonary fibrosis; therapeutics