The Supercarbonate Apatite-MicroRNA Complex Inhibits Dextran Sodium Sulfate-Induced Colitis

Tadafumi Fukata, Tsunekazu Mizushima, Junichi Nishimura, Daisuke Okuzaki, Xin Wu, Haruka Hirose, Yuhki Yokoyama, Yui Kubota, Kazuya Nagata, Naoto Tsujimura, Akira Inoue, Norikatsu Miyoshi, Naotsugu Haraguchi, Hidekazu Takahashi, Taishi Hata, Chu Matsuda, Hisako Kayama, Kiyoshi Takeda, Yuichiro Doki, Masaki MoriHirofumi Yamamoto

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

Abstract

The incidence of inflammatory bowel disease (IBD) is increasing. Nucleic acid-based medicine has potential as a next-generation treatment, but it is rarely successful with IBD. The aim of this study was to establish a microRNA-based therapy in an IBD model. For this purpose, we used microRNA-29 (miR-29) and a supercarbonate apatite (sCA) nanoparticle as a drug delivery system. Injection of sCA-miR-29a-3p or sCA-miR-29b-3p into mouse tail veins markedly prevented and restored inflammation because of dextran sulfate sodium (DSS)-induced colitis. RNA sequencing analysis revealed that miR-29a and miR-29b could inhibit the interferon-associated inflammatory cascade. Subcutaneous injection of sCA-miR-29b also potently inhibited inflammation, and it efficiently targeted CD11c+ dendritic cells (DCs) among various types of immune cells in the inflamed mucosa. RT-PCR analysis indicated that the miR-29 RNAs in CD11c+ DCs suppressed the production of interleukin-6 (IL-6), transforming growth factor β (TGF-β), and IL-23 subunits in DSS-treated mice. This may inhibit Th17 differentiation and subsequent activation, which is critical in IBD pathogenesis. In vivo experiments using a non-natural artificial microRNA sequence revealed that targeting of DCs in the inflamed colon is an exceptional feature of sCA. This study suggests that sCA-miR-29s may open a new avenue in nucleic acid-based medicine for IBD treatment.

Original languageEnglish
Pages (from-to)658-671
Number of pages14
JournalMolecular Therapy - Nucleic Acids
Volume12
DOIs
Publication statusPublished - Sep 7 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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