Elucidation of the functions of long non-coding RNA regulating cardiac hypertrophy and failure
Publicly Offered Research
Project Area | Neo-taxonomy of noncoding RNAs |
Project/Area Number |
17H05599
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Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
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Research Institution | Kyoto University |
Principal Investigator |
尾野 亘 京都大学, 医学研究科, 准教授 (00359275)
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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 |
¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Fiscal Year 2018: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2017: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
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Keywords | 心肥大 / 心不全 / 非コードRNA / long non-coding RNA |
Outline of Annual Research Achievements |
非コードRNAの多くを占める長鎖非コードRNA (lncRNA)に関しては、心不全において多くのlncRNA発現が変化することは知られているものの、個々の機能は未知である。我々は、心肥大、心不全をきたしたマウス心臓で有意に上昇する長鎖非コードRNAを網羅的に解析し、その機能を検討することとした。まず、マウス大動脈縮窄モデルを作成し、心肥大、心不全心で高発現していたlong intergenic non-coding RNA(lincRNA)を同定し、lincRNA-Hypertrophy1-10と名づけた。中でも、lincRNA-hypertrophy5は、心筋と骨格筋に特異的に発現するlincRNAである。 まず、RACE法にてこの全長を明らかにした。次にこの欠損マウスを作製したところ、野生型マウスに比較して心臓が小さく、また心臓に圧負荷をかけると代償できずに心不全を呈した。ビオチン化lincRNA-hypertrophy5と肥大心より抽出した核タンパクを結合させ、回収したタンパク質を質量分析で解析したところ、最も特異的に結合するタンパク質は、PURalphaというDNA/RNA結合タンパク質であった。lincRNA-hypertrophy5欠損マウスにおいては、PURalphaが過剰に働くことがミオシン重鎖蛋白の減少と線維芽細胞の減少、さらに心筋細胞の縮小につながることが明らかとなった。さらにヒト心筋生検組織におけるlincRNA-hypertrophy5発現を確認したところ、心機能の悪化とともに発現が減少しており、lincRNA-hypertrophy5発現が心機能を保持している可能性が示唆された。
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Research Progress Status |
平成30年度が最終年度であるため、記入しない。
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Strategy for Future Research Activity |
平成30年度が最終年度であるため、記入しない。
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Report
(2 results)
Research Products
(29 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] MicroRNA-33 regulates the population of peripheral inflammatory Ly6Chigh monocytes through dual pathways.2018
Author(s)
Baba O, Horie T, Nakao T, Hakuno D, Nakashima Y, Nishi H, Kuwabara Y, 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: 印刷中
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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[Journal Article] Imbalanced expression of polycistronic miRNA in acute myeloid leukemia.2017
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
Int J Hematol.
Volume: 106
Issue: 6
Pages: 811-819
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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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 decompensation.2017
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 Failure
Volume: 4
Issue: 2
Pages: 112-121
DOI
Related Report
Peer Reviewed / Open Access
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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
PLoS One
Volume: 12(3)
Issue: 3
Pages: e0172798-e0172798
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 Cholesterol.2016
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: -
Issue: 5
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)
Ono K, Nishino T, Horie T, Kuwabara Y, Nakao T, Nishiga M, Ide Y, Nakazeki F, Koyama S, Kimura M, Kimura T.
Organizer
43rd Naito Conference Noncoding RNA:Biology, Chemistry, & Diseases
Related Report
Int'l Joint Research
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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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