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
N1 - Funding Information:
This study was supported by the Japan Society for The Promotion of Science , JSPS KAKENHI Grant-in-Aid for Challenging Exploratory Research JP 16K15590 , and a research grant from The Osaka Medical Research Foundation for Intractable Diseases to H.Y.
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 -