Elucidation of the functions of miR-33a/b in cholesterol homeostasis
Project/Area Number |
23390211
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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 |
Circulatory organs internal medicine
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Research Institution | Kyoto University |
Principal Investigator |
ONO KOH 京都大学, 医学(系)研究科(研究院), 講師 (00359275)
|
Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Tomoyuki 関西医科大学, 医学部薬理学 (20362527)
|
Co-Investigator(Renkei-kenkyūsha) |
KAKEYA Hideaki 京都大学, 大学院・薬学研究科 (00270596)
SATO Fumiaki 京都大学, 大学院・薬学研究科 (20467426)
HORIE Takahiro 京都大学, 大学院・医学研究科循環器内科 (20565577)
|
Project Period (FY) |
2011-11-18 – 2014-03-31
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Project Status |
Completed (Fiscal Year 2013)
|
Budget Amount *help |
¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
|
Keywords | マイクロRNA / HDL-C / 動脈硬化 / ABCA1 / SREBP-2 / SREBP-1 / 脂肪肝 / 動脈瘤 / 心肥大 |
Research Abstract |
MicroRNAs (miRs) are small non-protein-coding RNAs that bind to specific mRNAs and inhibit translation or promote mRNA degradation. Recent reports, including ours, have indicated that miR-33 located within the intron of sterol regulatory element binding protein (SREBP) 2 controls cholesterol homeostasis and can be a potential therapeutic target for the treatment of atherosclerosis. Here we show that deletion of miR-33 results in marked worsening of high fat diet-induced obesity and liver steatosis. Using miR-33-/-Srebf1+/- mice we demonstrate that SREBP-1 is a target of miR-33 and that the mechanisms leading to obesity and liver steatosis in miR-33-/- mice involve enhanced expression of SREBP-1. These results elucidate a novel interaction between SREBP-1 and SREBP-2 mediated by miR-33 in vivo.
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Report
(4 results)
Research Products
(72 results)
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[Journal Article] Myocardial expression level of neural cell adhesion molecule correlates with reduced left ventricular function in human cardiomyopathy2014
Author(s)
Nagao K, Sowa N, Inoue K, Tokunaga M, Fukuchi K, Uchiyama K, Ito H, Hayashi F, Makita T, Inada T, Tanaka M, Kimura T, and Ono K
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Journal Title
Circulation; Heart Failur
Volume: 7
Issue: 2
Pages: 351-8
DOI
Related Report
Peer Reviewed
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[Journal Article] MicroRNA-33 regulates sterol regulatory element-binding protein 1 expression in mice.2013
Author(s)
Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Sowa N, Yahagi N, Shimano H, Matsumura S, Inoue K, Marusawa H, Nakamura T, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K
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Journal Title
Nat Commun.
Volume: 4:2883
Issue: 1
Pages: 2883-2883
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] CREDO-Kyoto PCI/CABG registry cohort-2 investigators. Impact of polyvascular disease on clinical outcomes in patients undergoing coronary revascularization : An observation from the CREDO-Kyoto Registry Cohort-22013
Author(s)
Morikami Y, Natsuaki M, Morimoto T, Ono K, Nakagawa Y, Furukawa Y, Sakata R, Aota M, Okada Y, Onoe M, Kawasuji M, Koshiji T, Nakajima H, Nishizawa J, Yamanaka K, Yamamoto H, Kimura T
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Journal Title
Atherosclerosis
Volume: 228
Issue: 2
Pages: 426-31
DOI
Related Report
Peer Reviewed
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[Journal Article] Metastasis-associated protein, S100A4 mediates cardiac fibrosis potentially through the modulation of p53 in cardiac fibroblasts2013
Author(s)
Tamaki Y, Iwanaga Y, Niizuma S, Kawashima T, Kato T, Inuzuka Y, Horie T, Morooka H, Takase T, Akahashi Y, Kobuke K, Ono K, Shioi T, Sheikh SP, Ambartsumian N, Lukanidin E, Koshimizu TA, Miyazaki S, Kimura T
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Journal Title
J Mol Cell Cardiol
Volume: 57
Pages: 72-81
DOI
Related Report
Peer Reviewed
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[Journal Article] Long-Term Outcomes After Percutaneous Coronary Intervention for Chronic Total Occlusion (from the CREDO-Kyoto Registry Cohort-2)2013
Author(s)
5: Yamamoto E, Natsuaki M, Morimoto T, Furukawa Y, Nakagawa Y, Ono K, Mitsudo K, Nobuyoshi M, Doi O, Tamura T, Tanaka M, Kimura T; CREDO-Kyoto PCI/CABG Registry Cohort-2 Investigators.
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Journal Title
Am J Cardiol.
Volume: 112
Issue: 6
Pages: 767-74
DOI
Related Report
Peer Reviewed
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[Journal Article] Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Plays an Important Role in Vascular Inflammation in Current Smokers.2013
Author(s)
6: Takanabe-Mori R, Ono K, Wada H, Takaya T, Ura S, Yamakage H, Satoh-Asahara N, Shimatsu A, Takahashi Y, Fujita M, Fujita Y, Sawamura T, Hasegawa K.
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Journal Title
J Atheroscler Thromb.
Volume: 20
Pages: 585-90
Related Report
Peer Reviewed
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[Journal Article] MicroRNA-33-deficiency reduces the progression of atherosclerotic plaque in apoE-/- mice2012
Author(s)
Horie T, Baba O, Kuwabara Y, Chujo Y, Watanabe S, Kinoshita M, Horiguchi M, Nakamura T, Chonabayashi K, Hishizawa M, Hasegawa K, Kume N, Yokode M, Kita T, Kimura T, Ono K
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Journal Title
JAm Heart Assoc
Volume: 1
Issue: 6
DOI
Related Report
Peer Reviewed
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[Journal Article] MicroRNA 26b Encoded by the Intron of Small CTD Phosphatase (SCP) 1 Has an Antagonistic Effect on its Host Gene2012
Author(s)
Sowa N, Horie T, Kuwabara Y, Baba O, Watanabe S, Nishi H, Kinoshita M, Takanabe-Mori R, Wada H, Shimatsu A, Hasegawa K, Kimura T, and Ono K
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Journal Title
Journal ofCellular Biochem.
Volume: 113
Issue: 11
Pages: 3455-65
DOI
Related Report
Peer Reviewed
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[Journal Article] Highly purified eicosapentaenoic acid increases interleukin-10 levels of peripheral blood monocytes in obese patients with dyslipidemia2012
Author(s)
N. Satoh-Asahara, A. Shimatsu, Y. Sasaki, H. Nakaoka, A. Himeno, M. Tochiya, S. Kono, T. Takaya, K. Ono, H. Wada, T. Suganami, K. Hasegawa, Y. Ogawa
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Journal Title
Diabetes Care
Volume: 35
Issue: 12
Pages: 2631-2639
DOI
Related Report
Peer Reviewed
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[Journal Article] Increased microRNA-1 and microRNA-133a levels in serum of patients with cardiovascular disease indicate myocardial damage2011
Author(s)
Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Kinoshita M, Watanabe S, Baba O, Kojima Y, Shizuta S, Imai M, Tamura T, Kita T, Kimura T
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Journal Title
Circ Cardiovasc Genet
Volume: 4
Issue: 4
Pages: 446-454
DOI
Related Report
Peer Reviewed
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[Journal Article] Comparison of Three-Year Clinical Outcomes after Sirolimus-eluting Stent Implantation among Insulin-treated Diabetic, Non-insulin-treated Diabetic and Non-diabetic Patients From the j-Cypher Registry2011
Author(s)
Tada T, Kimura T, Morimoto T, Ono K, Furukawa Y, Nakagawa Y, Nakashima H, Ito A, Shiode N, Namura M, Inoue N, Nishikawa H, Nakao K, Mitsudo K
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Journal Title
Am J Cardiol
Volume: 107
Issue: 8
Pages: 1155-62
DOI
Related Report
Peer Reviewed
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[Presentation] MicroRNA-33 encoded by an intron of sterol regulatory element-binding protein-2 (Srebp2) regulates Srebp1 in vivo2014
Author(s)
Horie T, Nishino T, Baba O, Kuwabara Y, Nakao T, Nishiga M, Usami S, Izuhara M, Sowa N, Yahagi N, Shimano H, Hasegawa K, Kume N Yokode M, Kita T, Kimura T, Ono K
Organizer
The 18th International Vascular Biology Meeting
Place of Presentation
Kyoto
Year and Date
2014-04-14
Related Report
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[Presentation] MicroRNA-451 Exacerbates Lipotoxicity in Neonatal Rat Cardiomyocytes, and High Fat Diet Induced Cardiac Hypertrophy in Mice through LKB1/AMPK Pathway2014
Author(s)
Yasuhide Kuwabara,Takahiro Horie, Osamu Baba, Shin Watanabe, Masayasu Izuhara, Tetsushi Nakao, Shunsuke Usami, Tomohiro Nishino, Masataka Nishiga, Toru Kita, Takeshi Kimura, Koh Ono
Organizer
第78回日本循環器学会学術集会
Place of Presentation
東京
Related Report
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[Presentation] Shock Reduction Strategies in High Energy Devices.2014
Author(s)
Satoshi Shizuta, Takahiro Doi , Mitsuhiko Yahata , Tetsuma Kawaji , Kentaro Nakai , Hiroaki Sugiyama , Koji Goto , Takeru Makiyama , Koh Ono , Tetsuo Shioi , Takeshi Kimura
Organizer
第78回日本循環器学会学術集会
Place of Presentation
東京
Related Report
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[Presentation] MicroRNA-33 Encoded by an Intron of Sterol Regulatory Element-Binding Protein 2 (Srebp2) Regulates Srebp1 in vivo.2014
Author(s)
Takahiro Horie, Tomohiro Nishino, Osamu Baba, Yasuhide Kuwabara, Tetsushi Nakao, Masataka Nishiga, Shunsuke Usami, Masayasu Izuhara, Naoya Sowa, Naoya Yahagi, Hitoshi Shimano, Masayuki Yokode, Toru Kita, Takeshi Kimura, Koh Ono
Organizer
第78回日本循環器学会学術集会
Place of Presentation
東京
Related Report
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[Presentation] MicroRNA-1 and microRNA-133a elevations in serum of patients with cardiovascular disease indicate the existence of myocardial damage2011
Author(s)
Kuwabara Y, Ono K, Horie T, Nishi H, Watanabe S, Kinoshita M, Baba O, Chujo Y, Nagao K, Kojima Y, Kita T, Kimura T
Organizer
American Heart Association Annual Scientific Sessions
Place of Presentation
Orlando, Florida
Related Report
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[Presentation] Neural cell adhesion molecule is a cardioprotective factor upregulated by metabolic stress2011
Author(s)
Nagao K, Ono K, Horie T, Tamaki Y, Iwanaga Y, Makita T, Inada T, Tanaka M, Kita T, Kimura T
Organizer
European Society of Cardiology Congress
Place of Presentation
Paris, France
Related Report
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