Elucidation of the functions of miR-33a/b in atherogenesis
| Project/Area Number |
17K16002
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | マイクロRNA / 動脈硬化症 / HDL / 核酸製剤 / HDL-C / 慢性炎症 / 新規核酸製剤 / 脂質代謝 |
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| Outline of Final Research Achievements |
Small non-coding RNA, called microRNA (miR), regulate gene expression precisely and it has been clear that microRNAs are involved in various kinds of disease mechanisms. Previously, we showed that miR-33a which is located in the intron of SREBP2 regulates intracellular cholesterol homeostasis and HDL cholesterol formation and atherosclerotic formation in mouse. Human have another family member of miR-33, miR-33b in addition to miR-33a. The function of miR-33b remains largely unknown. In this study, we explored the impact of miR-33b on atherosclerosis formation. miR-33b knock-in under apoE deficient mice background showed increased atherosclerosis formation via down-regulation of serum HDL levels and phenotypic changes of macrophages. These results indicated that miR-33b could become the new target of the arteriosclerosis treatment.
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| Academic Significance and Societal Importance of the Research Achievements |
動脈硬化症は心血管疾患の主因の一つである。現在の治療法は、高血圧・脂質代謝異常・耐糖能異常等の危険因子への介入である。超高齢化社会である我が国では未だ心血管疾患は主要な死因であり、新規予防法・治療法の開発が不可欠である。特に、HDL-コレステロールの増加や、慢性炎症の抑制を目指す治療法が期待されるものの詳細な分子機構が未解明であり、実現に至っていない。今回内在性の小さなRNAの一つ、miR-33bがHDL-コレステロール合成やその機能、また炎症細胞を介して炎症形成に重要であること、結果的に動脈硬化を進展させることを明らかとした。今後、miR-33bの抑制が新たな動脈硬化治療法として期待される。
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Report
(3 results)
Research Products
(13 results)
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[Journal Article] Loss of periostin ameliorates adipose tissue inflammation and fibrosis in vivo2018
Author(s)
Nakazeki Fumiko、Nishiga Masataka、Horie Takahiro、Nishi Hitoo、Nakashima Yasuhiro、Baba Osamu、Kuwabara Yasuhide、Nishino Tomohiro、Nakao Tetsushi、Ide Yuya、Koyama Satoshi、Kimura Masahiro、Tsuji Shuhei、Sowa Naoya、Yoshida Shigeo、Conway Simon J.、Yanagita Motoko、Kimura Takeshi、Ono Koh
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Journal Title
Scientific Reports
Volume: 8
Issue: 1
Pages: 8553-8553
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] MicroRNA-33 regulates the population of peripheral inflammatory Ly6Chigh monocytes through dual pathways.2018
Author(s)
Baba O, Horie T, Hakuno D, Nakashima Y, Nishi H, Kuwabara Y, Nakao T, Nishiga M, Nishino T, Ide Y, Nakazeki F, Koyama S, Kimura M, Hanada R, Kawahara M, Kimura T, and Ono K.
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Journal Title
Mol Cell Biol.
Volume: 38
Issue: 14
Pages: 1-17
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Genetic Ablation of MicroRNA-33 Attenuates Inflammation and Abdominal Aortic Aneurysm Formation via Several Anti-Inflammatory Pathways.2017
Author(s)
Nakao T, Horie T, Baba O, Nishiga M, Nishino T, Izuhara M, Kuwabara Y, Nishi H, Usami S, Nakazeki F, Ide Y, Koyama S, Kimura M, Sowa N, Ohno S, Aoki H, Hasegawa K, Sakamoto K, Minatoya K, Kimura T, Ono K.
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Journal Title
Arterioscler Thromb Vasc Biol.
Volume: 37
Issue: 11
Pages: 2161-2170
DOI
Related Report
Peer Reviewed / Open Access
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