Elucidating the role of microRNA-33 in chronic inflammation, fibrosis, and heart failure

• Project/Area Number: 16H06900
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto University
• Principal Investigator: Nishiga Masataka 京都大学, 医学研究科, 医員 (00782393)
• Project Period (FY): 2016-08-26 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 心不全 / 線維化 / 動脈硬化 / microRNA / 循環器・高血圧 / 内科

Outline of Final Research Achievements

MicroRNAs are small non-protein-coding RNAs (20-24 bp) that bind to specific mRNAs and inhibit translation or promote mRNA degradation. We have been focusing on miR-33 which decreases HDL-C and promotes atherosclerosis, and it is a potential therapeutic target against atherosclerosis. In this study, we clarified that miR-33 is also involved in heart failure. We used pressure-overload mouse model and found that miR-33 has roles dominantly in cardiac fibroblasts and is involved in cardiac fibrosis. The results show that atherosclerosis and heart failure share mechanisms that can be novel therapeutic targets.

Research Products

• [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.
  • Journal Title: Circ Res. Volume: - Issue: 5 Pages: 835-847
  • DOI: 10.1161/circresaha.116.309528
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] MicroRNA-33 controls adaptive fibrotic response in the remodeling heart by preserving lipid raft cholesterol (2017)
  • Author(s): Masataka Nishiga, Takahiro Horie, Yasuhide Kuwabara, Kazuya Nagao, Tetsushi Nakao, Tomohiro Nishino, Daihiko Hakuno, Yasuhiro Nakashima, Hitoo Nishi, Fumiko Nakazeki, Yuya Ide, Satoshi Koyama, Masahiro Kimura, Toru Kita, Takeshi Kimura, Koh Ono
  • Organizer: KEYSTONE SYMPOSIA RNA-Based Approaches in Cardiovascular Disease
  • Place of Presentation: Keystone, Colorado, USA
  • Year and Date: 2017-03-26
  • Int'l Joint Research
• [Presentation] MicroRNA-33 controls adaptive fibrotic response in the remodeling heart by preserving lipid raft cholesterol (2017)
  • Author(s): Masataka Nishiga, Koh Ono
  • Organizer: KEYSTONE SYMPOSIA RNA-Based Approaches in Cardiovascular Disease (X8)
  • Int'l Joint Research
• [Presentation] MicroRNA-33は脂質ラフトの維持を介して代償性の心臓線維化を促進する (2016)
  • Author(s): 西賀雅隆、堀江貴裕、桑原康秀、長央和也、中尾哲史、西野共達、長谷川浩二、北徹、木村剛、尾野亘
  • Organizer: 第20回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-16
• [Presentation] MicroRNA-33は脂質ラフト維持を介して心臓線維化を促進する (2016)
  • Author(s): 西賀雅隆、堀江貴裕、桑原康秀、長央和也、中尾哲史、西野共達、中関典子、井手裕也、小山智史、北徹、木村剛、尾野亘
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] MicroRNA-33 Maintains Cellular Cholesterol Content in Fibroblasts and Fibrotic Response in Heart (2016)
  • Author(s): Masataka Nishiga, Takahiro Horie, Yasuhide Kuwabara, Osamu Baba, Tetsushi Nakao, Tomohiro Nishino, Daihiko Hakuno, Yasuhiro Nakashima, Kazuya Nagao, Koji Hasegawa, Toru Kita, Takeshi Kimura, Koh Ono
  • Organizer: AHA 2016 Scientific Sessions
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] MicroRNA-33 promotes cardiac fibrosis through maintaining cellular lipid contents (2016)
  • Author(s): 西賀雅隆、堀江貴裕、桑原康秀、木村剛、尾野亘
  • Organizer: 第20回日本心不全学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2016-10-07