Investigations for lincRNA functions involved in cardiac remodeling.

• Project/Area Number: 24890094
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto University
• Principal Investigator: KUWABARA Yasuhide 京都大学, 医学(系)研究科(研究院), 医員 (60632099)
• Project Period (FY): 2012-08-31 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 循環器内科学 / 分子細胞生物学 / 非コーディングRNA / 心肥大 / 心不全 / lincRNA

Research Abstract

In the present study, we focused on the lincRNAs, a non-coding RNA, which may be involved in cardiac hypertrophy. We screened lincRNAs which were upregulated in mouse heart subjected to transverse aortic constriction, and identified three lincRNAs. In the present study, we tried to clarify the functions of the lincRNAs. Firstly, we overexpressed the lincRNAs in neonatal mouse cardiomyocytes, and found that cardiomyocyte hypertrophy was induced. Also, we demonstrated that ANP and BNP, markers of cardiac hypertrophy, were significantly increased when the two lincRNAs were overexpressed. Furthermore, we sought to evaluate whether a lincRNA bound to microRNAs. We found that lincRNA could bind to some microRNAs that play inhibitory role to hypertrophy. Finally, we revealed that protein level of cyclin was significantly increased in neonatal cardiomyocytes overexpressed the lincRNA. These results indicate that lincRNAs may be involved in cardiac hypertrophy.

Research Products

• [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
  • Journal Title: Nat Commun. Volume: 4 Pages: 2883-2883
  • NAID: 120005349007
• [Journal Article] MicroRNAs and Lipoprotein Metabolism (2013)
  • Author(s): Horie T, Baba O, Kuwabara Y, Yokode M, Kita T, Kimura T, Ono K
  • Journal Title: J Atheroscler Thromb. Volume: 21 Pages: 17-22
  • NAID: 130004845461
• [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
  • Journal Title: Nat Commun. Volume: 4:2883 Issue: 1 Pages: 2883-2883
  • DOI: 10.1038/ncomms3883
  • NAID: 120005349007
  • Peer Reviewed / Open Access
• [Journal Article] MicroRNAs and Lipoprotein Metabolism. (2013)
  • Author(s): Horie T, Baba O, Kuwabara Y, Yokode M, Kita T, Kimura T, Ono K.
  • Journal Title: J Atheroscler Thromb. Volume: 21 Pages: 17-22
  • NAID: 130004845461
  • Peer Reviewed
• [Journal Article] MicroRNA-33-deficiency reduces the progression of atherosclerotic plaque in apoE-/- mice (2012)
  • 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, and Ono K
  • Journal Title: J Am Heart Assoc. Volume: 1
• [Journal Article] MicroRNA 26b Encoded by the Intron of Small CTD Phosphatase (SCP) 1 Has an Antagonistic Effect on its Host Gene (2012)
  • 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
  • Journal Title: J Cell Biochem. Volume: 113 Pages: 3455-65
• [Presentation] MicroRNA-451 Exacerbates Lipotoxicity in Caridomyocytes and High Fat Diet-Induced Cardiac Hypertrophy in Mice Through Suppression of the LKB1/AMPK Pathway (2014)
  • Author(s): Kuwabara Y, Horie T, Baba O, Watanabe Shin, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Yuya Ide, Fumiko Nakazeki, Kimura T, Ono K
  • Organizer: The 78^<th> Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 東京国際フォーラム、東京
• [Presentation] microRNA-451はLKB1-AMPK経路を抑制することで、ラット心筋細胞において細胞障害を、生体においては高脂肪食誘導性心肥大を誘導する (2014)
  • Author(s): 桑原康秀、堀江貴裕、馬場理、出原正康、宇佐美俊輔、中尾哲史、西賀雅隆、西野共達、井手裕也、中関典子、木村剛、尾野亘
  • Organizer: 新学術領域転写代謝システム冬の若手ワークショップ2014
  • Place of Presentation: 磯部、群馬
• [Presentation] MicroRNA-451 Exacerbates Lipotoxicity in Caridomyocytes and High Fat Diet-Induced Cardiac Hypertrophy in Mice Through Suppression of the LKB1/AMPK Pathway. (2014)
  • Author(s): Kuwabara Y, Horie T, Baba O, Watanabe Shin, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Yuya Ide, Fumiko Nakazeki, Kimura T, Ono K.
  • Organizer: The 78th Annual Scientific Meeting of the Japanese Circulation Society.
  • Place of Presentation: 東京
• [Presentation] microRNA-451はLKB1-AMPK経路を抑制することで、ラット心筋細胞において細胞障害を、生体においては高脂肪食誘導性心肥大を誘導する。 (2014)
  • Author(s): 桑原康秀、堀江貴裕、馬場理、出原正康、宇佐美俊輔、中尾哲史、西賀雅隆、西野共達、井手裕也、中関典子、木村剛、尾野亘.
  • Organizer: 新学術領域 転写代謝システム 冬の若手ワークショップ 2014.
  • Place of Presentation: 群馬
• [Presentation] 循環器疾患におけるバイオマーカーとしての血清中microRNA (2013)
  • Author(s): 桑原康秀、尾野亘、堀江貴裕、ガーボル•バジョー、渡邉真、馬場理、出原正康、宇佐美俊輔、中尾哲史、西賀雅隆、西野共達、井手裕也、中関典子、木村剛
  • Organizer: 第115回日本循環器学会近畿地方会
  • Place of Presentation: 京都
  • Year and Date: 2013-06-15
• [Presentation] LincRNAs Regulated by Pressure-overload Induce Hypertrophy in Neonatal Mouse Ventricular Cardiomyocytes (2013)
  • Author(s): Kuwabara Y, Izuhara M, Horie T, Watanabe S, Baba O, Usami S, Nakao T, Nishiga M, Nishino T, Kita T, Kimura T, Ono K
  • Organizer: American Heart Association Annual Scientific Sessions 2013
  • Place of Presentation: Dallas, Texas, U.S.A.
• [Presentation] LincRNAs Regulated by Pressure-overload Induce Hypertrophy in Neonatal Mouse Ventricular Cardiomyocytes (2013)
  • Author(s): Kuwabara Y, Izuhara M, Horie T, Watanabe S, Baba O, Usami S, Nakao T, Nishiga M, Nishino T, Kita T, Kimura T, Ono K
  • Organizer: Cold Spring Harbor Laboratory Meeting. Metabolic Signaling & Disease : From Cell to Organism
  • Place of Presentation: Cold Spring Harbor, New York, U.S.A.
• [Presentation] MicroRNA-451 Exacerbates Lipotoxicity in Caridomyocytes and High Fat Diet-Induced Cardiac Hypertrophy in Mice Through Suppression of the LKB1/AMPK Pathway (2013)
  • Author(s): Kuwabara Y, Horie T, Baba O, Watanabe S, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Ide Y, Nakazeki F, Kimura T, Ono K
  • Organizer: International Symposium on Transcription and Metabolism
  • Place of Presentation: Awaji, Hyogo
• [Presentation] Elevated MicroRNA-1 and MicroRNA-133a Levels in Serum of Patients with Acute Coronary Syndrome Indicate the Myocardial Damage (2013)
  • Author(s): Kuwabara Y, Ono K, Horie T, Nishi H, Kinoshita M, Watanabe S, Nagao K, Baba O, Kita T, Kimura T
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] LincRNAs Regulated by Pressure-overload Induce Hypertrophy in Neonatal Mouse Ventricular Cardiomyocytes. (2013)
  • Author(s): Kuwabara Y, Izuhara M, Horie T, Watanabe S, Baba O, Usami S, Nakao T, Nishiga M, Nishino T, Kita T, Kimura T, Ono K.
  • Organizer: American Heart Association Annual Scientific Sessions 2013
  • Place of Presentation: Dallas, Texas, U.S.A.
• [Presentation] LincRNAs Regulated by Pressure-overload Induce Hypertrophy in Neonatal Mouse Ventricular Cardiomyocytes. Cold Spring Harbor Laboratory Meeting. (2013)
  • Author(s): Kuwabara Y, Izuhara M, Horie T, Watanabe S, Baba O, Usami S, Nakao T, Nishiga M, Nishino T, Kita T, Kimura T, Ono K.
  • Organizer: Cold Spring Harbor Laboratory Meeting. Metabolic Signaling & Disease: From Cell to Organism
  • Place of Presentation: Cold Spring Harbor, New York, U.S.A.
• [Presentation] MicroRNA-451 Exacerbates Lipotoxicity in Caridomyocytes and High Fat Diet-Induced Cardiac Hypertrophy in Mice Through Suppression of the LKB1/AMPK Pathway. (2013)
  • Author(s): Kuwabara Y, Horie T, Baba O, Watanabe S, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Ide Y, Nakazeki F, Kimura T, Ono K.
  • Organizer: International Symposium on Transcription and Metabolism
  • Place of Presentation: Awaji, Hyogo.
• [Presentation] MicroRNA-451 Exacerbates Lipotoxicity in Caridomyocytes and High Fat Diet-Induced Cardiac Hypertrophy in Mice Through Suppression of the LKB1/AMPK Pathway. (2013)
  • Author(s): Kuwabara Y, Horie T, Baba O, Watanabe S, Nishiga M, Usami S, Izuhara M, Nakao T, Nishino T, Ide Y, Nakazeki F, Kimura T, Ono K.
  • Organizer: International Symposium on Transcription and Metabolism, 2013
  • Place of Presentation: 兵庫
• [Presentation] MicroRNA 26b encoded by the introns of small CTD Phosphatases (SCPs) 1 has an antagonistic effect on its host gene and suppresses cardiac hypertrophy (2012)
  • Author(s): Kuwabara Y, Sowa N, Takahiro H, Baba O, Watanabe S, Nishi H, Hasegawa K, Kimura T, Ono K
  • Organizer: Cold Spring Harbor Laboratory Meeting. Regulatory and non-coding RNA
  • Place of Presentation: Cold Spring Harbor, New York, U.S.A.
• [Presentation] 心血管疾患患者血清におけるmicroRNA-1とmicroRNA-133aの上昇は心筋傷害を示唆する (2012)
  • Author(s): 桑原康秀
  • Organizer: 第49回日本臨床分子医学会学術集会
  • Place of Presentation: 京都
• [Presentation] 循環器疾患におけるバイオマーカーとしての血清中microRNA.
  • Author(s): 桑原康秀、尾野亘、堀江貴裕、ガーボル バジョー、渡邉真、馬場理、出原正康、宇佐美俊輔、中尾哲史、西賀雅隆、西野共達、井手裕也、中関典子、木村剛.
  • Organizer: 第115回日本循環器学会近畿地方会
  • Place of Presentation: 京都
• [Remarks]
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/metabolic/
• [Remarks] 京都大学医学部附属病院 循環器内科 心血管疾患分子機構解明グループ
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/metabolic/
• [Remarks] 京都大学医学部附属病院 循環器内科 心血管疾患分子機構解明グループ