Elucidation of global metabolic control mechanisms by microRNA-33a/b and development of specific regulatory strategy using artificial nucleic acid
Project/Area Number |
17H04177
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Cardiovascular medicine
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Research Institution | Kyoto University |
Principal Investigator |
Ono Koh 京都大学, 医学研究科, 准教授 (00359275)
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Co-Investigator(Kenkyū-buntansha) |
堀江 貴裕 京都大学, 医学研究科, 助教 (20565577)
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Project Status |
Completed (Fiscal Year 2019)
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Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2017: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
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Keywords | マイクロRNA / iPS細胞 / 核酸医薬 / 代謝 / iPSC / 人工核酸 |
Outline of Final Research Achievements |
We revealed that microRNA(miR)-33a/b have essential roles in low HDL-C, atherosclerosis, aortic aneurysm, fibrosis, non-alcoholic steatohepatitis, hypertension, Alzheimer disease, and activation of sympathetic nerve by the use of genetically modified induced pluripotent stem cell and mice. In these experiments, it was shown that miR-33a/b have different target genes in each cell or tissue. Moreover, we developed anti-miR-33a/b oligonucleotides that can selectively suppress the levels of miR-33a or -33b. We applied these oligonucleotides to several disease models and filed a patent for the treatment of aortic aneurysm. We are going to conduct clinical research to identify the clinical application of these oligonucleotides.
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Academic Significance and Societal Importance of the Research Achievements |
本研究により、microRNA-33a/bが低HDL-C、動脈硬化症、動脈瘤、線維化、NASHを含む慢性炎症、高血圧症、アルツハイマー症、交感神経系の活性化に共通する発症基盤であることが明らかになった。これは我々の作成した遺伝子改変マウスによってのみ明らかにすることができた点であり、学術的意義が高いと考えられる。さらに、miR-33aおよび33bを個別に制御できる架橋型人工核酸を開発し、複数の疾患モデルにおいて治療効果の検討を行っている。すでに大動脈瘤については治療法の特許申請中であり、今後さらに治療可能な疾患が増えることが予想されるため、臨床的・社会的意義も高いと考えられる。
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Report
(2 results)
Research Products
(28 results)
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[Journal Article] Prognostic Impact of Left Ventricular Ejection Fraction in Patients With Severe Aortic Stenosis.2018
Author(s)
Taniguchi T, Morimoto T, Shiomi H, Ando K, Kanamori N, Murata K, Kitai T, Kadota K, Izumi C, Nakatsuma K, Sasa T, Watanabe H, Kuwabara Y, Makiyama T, Ono K, Shizuta S, Kato T, Saito N, Minatoya K, Kimura T.
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Journal Title
JACC Cardiovasc Interv.
Volume: 11
Pages: 145-157
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Single-session versus staged procedures for elective multivessel percutaneous coronary intervention.2018
Author(s)
Toyota T, Morimoto T, Shiomi H, Yamaji K, Ando K, Ono K, Shizuta S, Saito N, Kato T, Kaji S, Furukawa Y, Nakagawa Y, Kadota K, Horie M, Kimura T,
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Journal Title
Heart (British Cardiac Society)
Volume: Nov 16.
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Impact of Transient or Persistent Contrast-induced Nephropathy on Long-term Mortality After Elective Percutaneous Coronary Intervention.2017
Author(s)
Abe M, Morimoto T, Nakagawa Y, Furukawa Y, Ono K, Kato T, Kadota K, Ando K, Ishii M, Masunaga N, Akao M, Kimura T.
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Journal Title
Am J Cardiol.
Volume: Dec 15;120(12):
Pages: 2146-2153
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Very long-term clinical outcomes after radiofrequency catheter ablation for atrial fibrillation: A large single-center experience.2017
Author(s)
Kawaji T, Shizuta S, Morimoto T, Aizawa T, Yamagami S, Yoshizawa T, Ota C, Onishi N, Sasaki Y, Yahata M, Nakai K, Hayano M, Nakao T, Hanazawa K, Goto K, Doi T, Ono K, Kimura T.
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Journal Title
Int J Cardiol.
Volume: 249
Pages: 204-213
DOI
Related Report
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[Journal Article] Genetic Ablation of MicroRNA-33 Attenuates Inflammation and Abdominal Aortic Aneurysm Formation via Several Anti-Inflammatory Pathways2017
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
Arteriosclerosis, Thrombosis, and Vascular Biology
Volume: 37
Pages: 2161-2170
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Imbalanced expression of polycistronic miRNA in acute myeloid leukemia2017
Author(s)
Kotaki R, Higuchi H, Ogiya D, Katahira Y, Kurosaki N, Yukihira N, Ogata J, Yamamoto H, Mohamad Alba S, Azhim A, Kitajima T, Inoue S, Morishita K, Ono K, Koyama-Nasu R, Kotani A.
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Journal Title
International Journal of Hematology
Volume: 106
Pages: 811-819
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Transradial versus transfemoral approach in patients undergoing primary percutaneous coronary intervention for ST-elevation acute myocardial infarction: insight from the CREDO-Kyoto AMI registry.2017
Author(s)
Yamashita Y, Shiomi H, Morimoto T, Yaku H, Kaji S, Furukawa Y, Nakagawa Y, Ando K, Kadota K, Abe M, Akao M, Nagao K, Shizuta S, Ono K, Kimura T
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Journal Title
Heart Vessels.
Volume: 32
Pages: 1936-1944
DOI
Related Report
Peer Reviewed
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[Journal Article] Asymptomatic Lower Extremity Deep Vein Thrombosis ― Clinical Characteristics, Management Strategies, and Long-Term Outcomes ―2017
Author(s)
Yamashita Y, Shiomi H, Morimoto T, Yoneda T, Yamada C, Makiyama T, Kato T, Saito N, Shizuta S, Ono K, Kimura T.
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Journal Title
Circ J
Volume: 81
Issue: 12
Pages: 1936-1944
DOI
NAID
ISSN
1346-9843, 1347-4820
Related Report
Peer Reviewed / Open Access
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[Journal Article] Dynamic changes of serum microRNA-122-5p through therapeutic courses indicates amelioration of acute liver injury accompanied by acute cardiac decompensation2017
Author(s)
Satoshi Koyama, Takashi Kuragaichi, Yukihito Sato, Yasuhide Kuwabara, Shunsuke Usami, Takahiro Horie, Osamu Baba, Daihiko Hakuno, Yasuhiro Nakashima, Tomohiro Nishino, Masataka Nishiga, Tetsushi Nakao, Hidenori Arai, Takeshi Kimura, Koh Ono
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Journal Title
ESC Heart Fail.
Volume: 4
Pages: 112-121
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease.2017
Author(s)
Morimoto T, Mineharu Y, Ono K, Nakatochi M, Ichihara S, Kabata R, Takagi Y, Cao Y, Zhao L, Kobayashi H, Harada K. H, Takenaka K, Funaki T, Yokota M, Matsubara T, Yamamoto K, Izawa H, Kimura T, Miyamoto S, Koizumi A
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Journal Title
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Prevention of Neointimal Formation Using miRNA-126-Containing Nanoparticle-Conjugated Stents in a Rabbit Model.2017
Author(s)
Izuhara M, Kuwabara Y, Saito N, Yamamoto E, Hakuno D, Nakashima Y, Horie T, Baba O, Nishiga M, Nakao T, Nishino T, Nakazeki F, Ide Y, Kimura M, Kimura T, Ono K.
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Journal Title
DOI
NAID
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Cardiac and Noncardiac Causes of Long-Term Mortality in ST-Segment-Elevation Acute Myocardial Infarction Patients Who Underwent Primary Percutaneous Coronary Intervention.2017
Author(s)
Yamashita Y, Shiomi H, Morimoto T, Yaku H, Furukawa Y, Nakagawa Y, Ando K, Kadota K, Abe M, Nagao K, Shizuta S, Ono K, Kimura T; CREDO-Kyoto AMI Registry Investigators.
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Journal Title
Circ Cardiovasc Qual Outcomes.
Volume: 10
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] MicroRNA-33 Controls Adaptive Fibrotic Response in the Remodeling Heart by Preserving Lipid Raft CholesterolNovelty and Significance2017
Author(s)
Nishiga M, Horie T, Kuwabara Y, Nagao K, Baba O, Nakao T, Nishino T, Hakuno D, Nakashima Y, Nishi H, Nakazeki F, Ide Y, Koyama S, Kimura M, Hanada R, Nakamura T, Inada T, Hasegawa K, Conway SJ, Kita T, Kimura T, Ono K.
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Journal Title
Circ Res
Volume: -
Pages: 835-847
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] Novel Long Intergenic Noncoding RNA, Lionheart, Guards the Heart from Pressure Overload2018
Author(s)
Kuwabara Y, Horie T, Baba O, Nishiga M, Nakao M, Nishino T, Nakazeki F, Koyama S, Kimura T, Ono K.
Organizer
第82回日本循環器学会
Related Report
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[Presentation] MicroRNA-33b promotes atherosclerotic plaque formation in Apoe-/- mice.2017
Author(s)
Nishino T, Horie T, Kuwabara Y, Nakao T, Nishiga M, Ide Y, Nakazeki F, Koyama S, Kimura M, Kimura T, Ono K
Organizer
American Heart Association Scientific Sessions 2017
Related Report
Int'l Joint Research
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