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 journalArticle

3 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

Fingerprint

Apatites
Dextran Sulfate
Colitis
MicroRNAs
Inflammatory Bowel Diseases
Dendritic Cells
Nucleic Acids
Inflammation
RNA Sequence Analysis
Interleukin-23
Transforming Growth Factors
Subcutaneous Injections
Drug Delivery Systems
Nanoparticles
Interferons
Tail
Veins
Interleukin-6
Colon
Mucous Membrane

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

Cite this

Fukata, T., Mizushima, T., Nishimura, J., Okuzaki, D., Wu, X., Hirose, H., ... Yamamoto, H. (2018). The Supercarbonate Apatite-MicroRNA Complex Inhibits Dextran Sodium Sulfate-Induced Colitis. Molecular Therapy - Nucleic Acids, 12, 658-671. https://doi.org/10.1016/j.omtn.2018.07.007

The Supercarbonate Apatite-MicroRNA Complex Inhibits Dextran Sodium Sulfate-Induced Colitis. / Fukata, Tadafumi; Mizushima, Tsunekazu; Nishimura, Junichi; Okuzaki, Daisuke; Wu, Xin; Hirose, Haruka; Yokoyama, Yuhki; Kubota, Yui; Nagata, Kazuya; Tsujimura, Naoto; Inoue, Akira; Miyoshi, Norikatsu; Haraguchi, Naotsugu; Takahashi, Hidekazu; Hata, Taishi; Matsuda, Chu; Kayama, Hisako; Takeda, Kiyoshi; Doki, Yuichiro; Mori, Masaki; Yamamoto, Hirofumi.

In: Molecular Therapy - Nucleic Acids, Vol. 12, 07.09.2018, p. 658-671.

Research output: Contribution to journalArticle

Fukata, T, Mizushima, T, Nishimura, J, Okuzaki, D, Wu, X, Hirose, H, Yokoyama, Y, Kubota, Y, Nagata, K, Tsujimura, N, Inoue, A, Miyoshi, N, Haraguchi, N, Takahashi, H, Hata, T, Matsuda, C, Kayama, H, Takeda, K, Doki, Y, Mori, M & Yamamoto, H 2018, 'The Supercarbonate Apatite-MicroRNA Complex Inhibits Dextran Sodium Sulfate-Induced Colitis', Molecular Therapy - Nucleic Acids, vol. 12, pp. 658-671. https://doi.org/10.1016/j.omtn.2018.07.007
Fukata, Tadafumi ; Mizushima, Tsunekazu ; Nishimura, Junichi ; Okuzaki, Daisuke ; Wu, Xin ; Hirose, Haruka ; Yokoyama, Yuhki ; Kubota, Yui ; Nagata, Kazuya ; Tsujimura, Naoto ; Inoue, Akira ; Miyoshi, Norikatsu ; Haraguchi, Naotsugu ; Takahashi, Hidekazu ; Hata, Taishi ; Matsuda, Chu ; Kayama, Hisako ; Takeda, Kiyoshi ; Doki, Yuichiro ; Mori, Masaki ; Yamamoto, Hirofumi. / The Supercarbonate Apatite-MicroRNA Complex Inhibits Dextran Sodium Sulfate-Induced Colitis. In: Molecular Therapy - Nucleic Acids. 2018 ; Vol. 12. pp. 658-671.
@article{60786ba8a966447b832b0d741b12edfc,
title = "The Supercarbonate Apatite-MicroRNA Complex Inhibits Dextran Sodium Sulfate-Induced Colitis",
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.",
author = "Tadafumi Fukata and Tsunekazu Mizushima and Junichi Nishimura and Daisuke Okuzaki and Xin Wu and Haruka Hirose and Yuhki Yokoyama and Yui Kubota and Kazuya Nagata and Naoto Tsujimura and Akira Inoue and Norikatsu Miyoshi and Naotsugu Haraguchi and Hidekazu Takahashi and Taishi Hata and Chu Matsuda and Hisako Kayama and Kiyoshi Takeda and Yuichiro Doki and Masaki Mori and Hirofumi Yamamoto",
year = "2018",
month = "9",
day = "7",
doi = "10.1016/j.omtn.2018.07.007",
language = "English",
volume = "12",
pages = "658--671",
journal = "Molecular Therapy - Nucleic Acids",
issn = "2162-2531",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - The Supercarbonate Apatite-MicroRNA Complex Inhibits Dextran Sodium Sulfate-Induced Colitis

AU - Fukata, Tadafumi

AU - Mizushima, Tsunekazu

AU - Nishimura, Junichi

AU - Okuzaki, Daisuke

AU - Wu, Xin

AU - Hirose, Haruka

AU - Yokoyama, Yuhki

AU - Kubota, Yui

AU - Nagata, Kazuya

AU - Tsujimura, Naoto

AU - Inoue, Akira

AU - Miyoshi, Norikatsu

AU - Haraguchi, Naotsugu

AU - Takahashi, Hidekazu

AU - Hata, Taishi

AU - Matsuda, Chu

AU - Kayama, Hisako

AU - Takeda, Kiyoshi

AU - Doki, Yuichiro

AU - Mori, Masaki

AU - Yamamoto, Hirofumi

PY - 2018/9/7

Y1 - 2018/9/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85050990281&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85050990281&partnerID=8YFLogxK

U2 - 10.1016/j.omtn.2018.07.007

DO - 10.1016/j.omtn.2018.07.007

M3 - Article

AN - SCOPUS:85050990281

VL - 12

SP - 658

EP - 671

JO - Molecular Therapy - Nucleic Acids

JF - Molecular Therapy - Nucleic Acids

SN - 2162-2531

ER -