Role of microRNAs on metabolic control in the heart

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590864
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: ONO Koh Kyoto University, 医学研究科, 講師 (00359275)
• Project Period (FY): 2008 – 2010
• Keywords: マイクロRNA / 心肥大 / 心不全 / 動脈硬化

Research Abstract

About 1000miRNAs have already been discovered in human and it is estimated that they can regulate more than 50% of genes. We have shown that specific miRNAs have function in cardiac hypertrophy, heart failure, and metabolic disorders. Some of miRNAs are good targets for the treatment of such disease conditions. We also revealed that circulating miR-1 and miR-133a can be used as biomarkers for myocardial injury and there is a possibility that they can affect in other cells/organs.

Research Products

• [Journal Article] Increased microRNA-1 and microRNA-133a Levels in Serum of Patients with Cardiovascular Disease Indicate the Existence of Myocardial Damage. (2011)
  • 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.
  • Journal Title: Circulation : Cardiovascular Genetics. in press
  • Peer Reviewed
• [Journal Article] MicroRNA links obesity and impaired glucose metabolism. (2011)
  • Author(s): Ono K.
  • Journal Title: Cell Res. in press
  • Peer Reviewed
• [Journal Article] MicroRNAs and Cardiovascular Diseases. (2011)
  • Author(s): Ono K, Kuwabara Y, Han J.
  • Journal Title: FEBS J. 278 Pages: 1619-33
  • Peer Reviewed
• [Journal Article] MicroRNA-27a regulates beta cardiac myosin heavy chain gene expression by targeting thyroid hormone receptor beta 1 in neonatal rat ventricular myocytes. (2011)
  • Author(s): Nishi H, Ono K, Horie T, Nagao K, Kinoshita M, Kuwabara Y, Watanabe S, Takaya T, Tamaki Y, Takanabe-Mori R, Wada H, Hasegawa K, Iwanaga Y, Kawamura T, Kita T, Kimura T.
  • Journal Title: Mol Cell Biol. 31 Pages: 744-55
  • Peer Reviewed
• [Journal Article] MicroRNA-33 encoded by an intron of Srebp2 regulates HDL in vivo Proc Natl (2010)
  • Author(s): Horie T, Ono K, Horiguchi M, Nishi H, Nakamura T, Nagao K, Kinoshita M, Kuwabara Y, Marusawa H, Iwanaga Y, Hasegawa K, Yokode M, Kimura T, Kita T.
  • Journal Title: Acad Sci USA. 107 Pages: 17321-6
  • Peer Reviewed
• [Journal Article] Regulation of adipocyte differentiation by activation of serotonin (5-HT) receptors 5-HT2AR and 5-HT2CR and involvement of microRNA-448-mediated repression of KLF5. (2010)
  • Author(s): Kinoshita M, Ono K, Horie T, Nagao K, Nishi H, Kuwabara Y, Takanabe-Mori R, Hasegawa K, Kita T, Kimura T.
  • Journal Title: Molecular Endoclinology. 24 Pages: 1978-87
  • Peer Reviewed
• [Journal Article] Acute Doxorubicin Cardiotoxicity Is Associated with miR-146a-induced Inhibition of the Neuregulin-ErbB (2010)
  • Author(s): Horie T, Ono K, Nishi H, Nagao K, Kinoshita M, Watanabe S, Kuwabara Y, Nakashima Y, Takanabe-Mori R, Nishi E, Hasegawa K, Kita T, Kimura T.
  • Journal Title: Pathway Cardiovascular Res. 87 Pages: 656-664
  • Peer Reviewed
• [Journal Article] MicroRNA-15b modulates cellular ATP levels and degenerates mitochondria via ARL2 in neonatal rat cardiac myocytes. (2010)
  • Author(s): Nishi H, Ono K, Iwanaga Y, Horie T, Nagao K, Takemura G, Kinoshita M, Kuwabara Y, Takanabe Mori R, Hasegawa K, Kita T, Kimura T.
  • Journal Title: J Biol Chem. 285 Pages: 4920-30
  • Peer Reviewed
• [Journal Article] Neural cell adhesion molecule is a cardioprotective factor up-regulated by metabolic stress. (2010)
  • Author(s): Nagao K, Ono K, Iwanaga Y, Tamaki Y, Kojima Y, Horie T, Nishi H, Kinoshita M, Kuwabara Y, Hasegawa K, Kita T, Kimura T.
  • Journal Title: Journal of Molecular and Cellular Cardiology. 48 Pages: 1157-68
  • Peer Reviewed
• [Journal Article] MicroRNA-133 regulates the expression of GLUT4 by targeting KLF15 and is involved in metabolic control in cardiac myocytes. (2009)
  • Author(s): Horie T, Ono K, Nishi H, Iwanaga Y, Nagao K, Kinoshita M, Kuwabara Y, Takanabe R, Hasegawa K, Kita T, Kimura T.
  • Journal Title: Biochem Biophys Res Commun. 389 Pages: 315-20
  • Peer Reviewed
• [Journal Article] MicroRNA-1 and MicroRNA-133 in Spontaneous Myocardial Differentiation of Mouse Embryonic Stem Cells. (2009)
  • Author(s): Takaya T, Ono K, Kawamura T, Takanabe R, Kaichi S, Morimoto T, Wada H, Kita T, Shimatsu A, Hasegawa K.
  • Journal Title: Circulation J. 73 Pages: 1492-7
  • Peer Reviewed
• [Journal Article] Up-regulated expression of microRNA-143 in association with obesity in adipose tissue of mice fed high-fat diet. (2008)
  • Author(s): Takanabe R, Ono K, Abe Y, Takaya T, Horie T, Wada H, Kita T, Satoh N, Shimatsu A, Hasegawa K.
  • Journal Title: Biochem Biophys Res Commun. 376 Pages: 728-32
  • Peer Reviewed
• [Presentation] Plenary session. (2011)
  • Author(s): Ono K.
  • Organizer: MicroRNA-33 Encoded by an Intron of Srebp2 Cooperates to Control HDL in Vivo.
  • Place of Presentation: 横浜市
  • Year and Date: 20110318-20110320
• [Presentation] Young Investigator's Award Finalists Lectures-2 (2011)
  • Author(s): Horie T, Ono K, Horiguchi M, Nishi H, Nakamura T, Nagao K, Kinoshita M, Kuwabara Y, Marusawa H, Iwanaga Y, Hasegawa K, Yokode M, Kimura T, Kita T.
  • Organizer: MicroRNA-33 Encoded by an Intron of Srebp2 Regulates HDL in vivo.
  • Place of Presentation: 横浜市
  • Year and Date: 20110318-20110320
• [Presentation] MiR-146a-induced Inhibition of Neuregulinl- (2011)
  • Author(s): Horie T, Ono K, Nishi H, Kinoshita M, Watanabe S, Kuwabara Y, Baba O, Mori R, Nagao K, Iwanaga Y, Nishi E, Hasegawa K, Kita T, Kimura T.
  • Organizer: ErbB4 Pathway may be Involved in Deterioration of Cardiotoxicity under Concurrent Chemotherapy with Doxorubicin and Trastuzumab.
  • Place of Presentation: 横浜市
  • Year and Date: 20110318-20110320
• [Presentation] Elevated MicroRNA-1 and MicroRNA- (2011)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Kinoshita M, Watanabe S, Baba O, Kita T, Kimura T.
  • Organizer: 133a Levels in Serum of Patients with Acute Cronary Syndrome Indicate the Myocardial Damage.
  • Place of Presentation: 横浜市
  • Year and Date: 20110318-20110320
• [Presentation] MicroRNA 26b family encoded by the introns of small CTD Phosphatases (SCPs) 1 to 3 suppresses phenylephrine-induced cardiomyocyte hypertrophy by targeting TRPC3/6 and GATA4 (2010)
  • Author(s): Ono K, Sowa N, Horie T, Hasegawa K, Kita T, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Chicago, Illinois
  • Year and Date: 20101113-20101117
• [Presentation] MiR-146a-induced inhibition of the neuregulin-ErbB4 pathway may be involved in deterioration of cardiotoxicity under concurrent chemotherapy with doxorubicin and Trastuzumab. (2010)
  • Author(s): Horie T, Ono K, Iwanaga Y, Nishi H, Nagao K, Kinoshita M, Watanabe S, Kuwabara Y, Nakashima Y, Takanabe-Mori R, Nishi E, Hasegawa K, Kita T, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Chicago, Illinois
  • Year and Date: 20101113-20101117
• [Presentation] MicroRNA-27a regulates beta-myocin heavy chain gene expression by targeting thyroid hormone receptor beta 1 in neonatal rat ventricular myocytes. (2010)
  • Author(s): Nishi H, Ono K, Horie T, Nagao K, Kinoshita M, Kuwabara Y, Baba O, Nakashima Y, Nagao K, Takanabe-Mori R, Hasegawa K, Kita T, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Chicago, Illinois
  • Year and Date: 20101113-20101117
• [Presentation] MicroRNA-1 and microRNA-133a are useful as early diagnostic biomarkers in patients with acute coronary syndrome. (2010)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Kinoshita M, Watanabe S, Nakashima Y, Nagao K, Kojima Y, Kita T, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Chicago, Illinois
  • Year and Date: 20101113-20101117
• [Presentation] MicroRNA-448 regulates adipocyte differentiation by targeting KLF5. (2010)
  • Author(s): Kinoshita M, Ono K, Kuwabara Y, Nishi H, Nagao K, Horie T, Mori R, Hasegawa K, Kita T, Kimura T
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都
  • Year and Date: 20100305-20100307
• [Presentation] Impact of microRNAs on cardiomyocyte metabolism. Topic 12 (2010)
  • Author(s): Ono K, Nishi H, Iwanaga Y, Horie T, Nagao K, Takemura G, Kinoshita M, Kuwabara Y, Takanabe-Mori R, Hasegawa K, Kita T, Kimura T
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都
  • Year and Date: 20100305-20100307
• [Presentation] MicroRNA-27a regulates beta cardiac myosin heavy chain gene expressions by targeting thyroid hormone receptor beta 1. (2010)
  • Author(s): Nishi H, Ono K, Horie T, Nagao K, Kinoshita M, Kuwabara Y, Mori-Takanabe R, Hasegawa K, Kita T, Kimura T
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都
  • Year and Date: 20100305-20100307
• [Presentation] MicroRNA-378, which exists intronic lesion of PGC-lbeta, deteriorates cardiomyocyte survival under oxidative stress. (2010)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Watanabe S, Kinoshita M, Kojima Y, Kita T, Kimura T
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都
  • Year and Date: 20100305-20100307
• [Presentation] microRNA-146-mediated reduction of ErbB4 is an early event in Doxorubicin-induced cardiomyocyte cell death. (2010)
  • Author(s): Horie T, Ono K, Nishi H, Nagao K, Kinoshita M, Kuwabara Y, takanabe R, Watanabe S, Kojima Y, Nakashima Y, Iwanaga Y, Hasegawa K, Kita T, Kimura T
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都
  • Year and Date: 20100305-20100307
• [Presentation] Neural cell adhesion molecule is a cardioprotective factor upregulated by metabolic stress. (2010)
  • Author(s): Nagao K, Ono K, Horie T, Kinoshita M, Nishi H, Tamaki Y, Kuwabara Y, Iwanaga Y, Kita T, Kimura T
  • Organizer: 第74回日本循環器学会
  • Place of Presentation: 京都
  • Year and Date: 20100305-20100307
• [Presentation] Acute doxorubicin cardiomyopathy is associated with miR-146a-induced inhibition of the neuregulin-ErbB4 pathway. (2009)
  • Author(s): Horie T, Ono K, lwanaga Y, Nishi H, Nagao K, Kinoshita M, Kuwabara Y, Takanabe-Mori R, Hasegawa K, Kita T, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Orlando, Florida
  • Year and Date: 20091114-20091118
• [Presentation] Neural cell adhesion molecule is a cardioprotective factor upregulated by metabolic stress. (2009)
  • Author(s): Nagao K, Ono K, Horie T, Nishi H, Kinoshita M, Kojima Y, Tamaki Y, Kuwabara Y, Iwanaga Y, Kita T, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Orlando, Florida
  • Year and Date: 20091114-20091118
• [Presentation] MicroRNA-15b, -16, 195, and-424, which have the same seed sequence, regulate ADP-rybosylation factor-like 2 and cellular ATP levels in neonatal rat cardiomyocytes (2009)
  • Author(s): Nishi H, Ono K, Horie T, Nagao K, Kinoshita M, Kuwabara-Y, Takanabe-Mori R, Hasegawa K, Takemura G, Iwanaga Y, Kita T, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Orlando, Florida
  • Year and Date: 20091114-20091118
• [Presentation] MicroRNA-378, which exists intronic lesion of PGC-lbeta, deteriorate cardiomyocyte survival under oxidative stress. (2009)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Nagao K, Watanabe S, Kojima Y, Kinoshita M, Mori R, Kita T, Kimura T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Orlando, Florida
  • Year and Date: 20091114-20091118
• [Presentation] Let-7/miR-98 family regulates the expression of GLUT4 by targeting Mef-2C in metabolic control of cardiomyocytes. (2009)
  • Author(s): Sowa N, Ono K, Horie T, Iwanaga Y, Nishi H, Nagao K, Kinoshita M, Takanabe-Mori R, Kita T, Kimura T, Hasegawa K
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: Orlando, Florida
  • Year and Date: 20091114-20091118
• [Presentation] NF-kB-dependent induction of microRNA-146 downregulates ErbB4 and may be involved in the development of cardiomyocyte survival. (2009)
  • Author(s): Horie T, Ono K, Iwanaga Y, Nishi H, Nagao K, Kinoshita M, Mori R, Kuwabara Y, Hasegawa K, Kita T
  • Organizer: 第73回日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 20090320-20090322
• [Presentation] Neural cell adhesion molecule is upregulated by metabolic stress and enhances the cardiomyocyte survival. (2009)
  • Author(s): Nagao K, Ono K, Horie T, Kinoshita M, Nishi H, Tamaki Y, Kuwabara Y, Iwanaga Y, Kita T.
  • Organizer: 第73回日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 20090320-20090322
• [Presentation] Neural cell adhesion molecule isupregulated by metabolic stress and enhances the cardiomyocyte survival rate through neurite-cardiomyocyte communication. (2008)
  • Author(s): Nagao K, Ono K, Horie T, Kojima Y, Nishi H, Kinoshita M, Kita T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: New Orleans, Louisiana
  • Year and Date: 20081108-20081112
• [Presentation] NF-kB-dependent induction of microRNA-146 downregulates ErbB4 and may be involved in the deterioration of cardiomyocyte survival. (2008)
  • Author(s): Horie T, Ono K, Iwanaga Y, Nishi H, Nagao K, Kinoshita M, Mori R, Hasegawa K, Kita T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: New Orleans, Louisiana
  • Year and Date: 20081108-20081112
• [Presentation] Upregulation of microRNA-27a, which downregulates retionoid X receptor a, controls cardiac myosin heavy chain gene expression in neonatal rat cardioyocyte. (2008)
  • Author(s): Nishi H, Ono K, Kinoshita M, Nagao K, Horie T, Takanabe R, Hasegawa K, Iwanaga Y, Kita T
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: New Orleans, Louisiana
  • Year and Date: 20081108-20081112
• [Presentation] Up-regulated expression of microRNA-143 in association with obesity in the adipose tissue of mice fed with high fat diet. (2008)
  • Author(s): Takanabe R, Ono K, Takaya T, Horie T, Wada H, Kita T, Shimatsu A, Hasegawa K
  • Organizer: American Heart Association Annual Scientific Sessions
  • Place of Presentation: New Orleans, Louisiana
  • Year and Date: 20081108-20081112
• [Book] Micro RNA-33を介したHDL-コレステロール調節のあらたなメカニズム.医学のあゆみ(237) (2011)
  • Author(s): 尾野亘、木村剛
  • Total Pages: 734-738
• [Book] miRNA-33は生体内でHDLコレステロールを制御する 実験医学(29(4)) (2011)
  • Author(s): 尾野亘、堀江貴裕、木村剛、北徹
  • Total Pages: 575-578
• [Book] SREBP2のイントロンにコードされるマイクロRNA-33は生体においてHDL形成を制御するTherapeutic Research(32(6)) (2011)
  • Author(s): 尾野亘
  • Total Pages: 773-776
• [Book] 「心筋梗塞モデル(小動物)」循環器疾患-疾患モデルの作成と利用 (2010)
  • Author(s): 尾野亘
  • Total Pages: 35-39
  • Publisher: Life Science Information center.
• [Book] Biology topics. MicroRNAと心疾患. Bio Clinica.(25(6)) (2010)
  • Author(s): 尾野亘、木村剛
  • Total Pages: 84-89
• [Remarks] ホームページ等
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/metabolic/