Novel form of miR-29b suppresses bleomycin-induced pulmonary fibrosis

Yuko Yamada; Masakatsu Takanashi; Katsuko Sudo; Shinobu Ueda; Shin-Ichiro Ohno; Masahiko Kuroda

doi:10.1371/journal.pone.0171957

Novel form of miR-29b suppresses bleomycin-induced pulmonary fibrosis

PLoS One. 2017 Feb 24;12(2):e0171957. doi: 10.1371/journal.pone.0171957. eCollection 2017.

Authors

Yuko Yamada¹, Masakatsu Takanashi¹, Katsuko Sudo², Shinobu Ueda¹, Shin-Ichiro Ohno¹, Masahiko Kuroda¹

Affiliations

¹ Department of Molecular Pathology, Tokyo Medical University, Shinjuku, Tokyo, Japan.
² Animal Research Center, Tokyo Medical University, Shinjuku, Tokyo, Japan.

Abstract

MicroRNA 29b (miR-29b) replacement therapy is effective for suppressing fibrosis in a mouse model. However, to develop clinical applications for miRNA mimics, the side effects of nucleic acid drugs have to be addressed. In this study, we focused on miRNA mimics in order to develop therapies for idiopathic pulmonary fibrosis. We developed a single-stranded RNA, termed "miR-29b Psh-match," that has a unique structure to avoid problems associated with the therapeutic uses of miRNAs. A comparison of miR-29b Psh-match and double-stranded one, termed "miR-29b mimic" indicated that the single-stranded form was significantly effective towards fibrosis according to both in vivo and in vitro experiments. This novel form of miR-29b may become the foundation for developing an effective therapeutic drug for pulmonary fibrosis.

MeSH terms

Administration, Inhalation
Animals
Bleomycin / adverse effects*
Fibroblasts / metabolism
Hydroxyproline / analysis
Male
Mice
Mice, Inbred C57BL
MicroRNAs / therapeutic use*
NIH 3T3 Cells
Pulmonary Fibrosis / chemically induced
Pulmonary Fibrosis / drug therapy*
Signal Transduction
Toll-Like Receptors / metabolism
Transforming Growth Factor beta / pharmacology

Substances

MIRN29 microRNA, mouse
MicroRNAs
Toll-Like Receptors
Transforming Growth Factor beta
Bleomycin
Hydroxyproline

Grants and funding

This research was supported in part by Grants-in-Aid for Scientific Research (B: 26296088) and (C: 16K09376) and a Grant-in-Aid for Exploratory Research (15K15100) from Japan Society for the Promotion of Science (JSPS) and supported in part by Strategic Research Foundation Grant-aided Project for Private Universities from the Ministry of Education, Culture, Sports, Science and Technology of Japan.