Nardilysin regulates sinus automaticity through transcription of HCN.

• Project/Area Number: 15K19376
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto University
• Principal Investigator: OHNO Mikiko 京都大学, 医学研究科, 助教 (10583198)
• Research Collaborator: NISHI Eiichiro 滋賀医科大学, 薬理学講座, 教授 (30362528)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 洞房結節自動能 / 心不全 / HCN / 転写因子

Outline of Final Research Achievements

Nardilysin is a multi-functional protein, which regulates ectodomain shedding of membrane anchored protein in the cell surface and transcription in the nucleus. NRDc knockout mice show bradycardia because of poor expression of HCN channels in the heart. HCN is one of the critical regulator for sinus automaticity. We found that NRDc regulates mRNA and protein expression of HCN4.
Furthermore, since HCN4 inhibitor is useful for heart failure in humans, we analyzed the significance of NRDc in the heart failure using mouse TAC (transverse aortic constriction) model.

Research Products

• [Journal Article] Nardilysin is required for maintaining pancreatic β-Cell Function. (2016)
  • Author(s): Nishi K, Sato Y, Ohno M, Hiraoka Y, Saijo S, Sakamoto J, Chen P-M, Morita Y, Matsuda S, Iwasaki K, Sugizaki K, Harada N, Mukumoto Y, Kiyonari H, Furuyama K, Kawaguchi Y, Uemoto S, Kita T, Inagaki N, Kimura T and Nishi E
  • Journal Title: Diabetes Volume: 65 Issue: 10 Pages: 3015-3027
  • DOI: 10.2337/db16-0178
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 基礎と臨床の橋渡しを目指して～新規ACSバイオマーカーの開発～ (2017)
  • Author(s): 大野美紀子
  • Organizer: 第81回日本循環器学会学術集会 第１回Travel Award for Women Cardiologists
  • Place of Presentation: 石川県立音楽堂外（石川県金沢市）
  • Year and Date: 2017-03-17
  • Invited
• [Presentation] Nardilysin is a Promising Biomarker for the Early Diagnosis of Acute Coronary Syndrome. (2017)
  • Author(s): Ohno M, Chen P-M, Hiwasa T, Nishi K, Saijo S, Sakamoto J, Morita Y, Watanabe S, Kuwabara Y, Ono K, Imai M, Inoue K, Murai T, Kita T, Kimura T, and Nishi E.
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 石川県立音楽堂外（石川県金沢市）
  • Year and Date: 2017-03-17
• [Presentation] Nardilysin is a Promising Biomarker for the Early Diagnosis of Acute Coronary Syndrome. (2016)
  • Author(s): Ohno M, Chen P-M, Hiwasa T, Nishi K, Saijo S, Sakamoto J, Morita Y, Watanabe S, Kuwabara Y, Ono K, Imai M, Inoue K, Murai T, Kita T, Kimura T, and Nishi E.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Nardilysin controls circulatory dynamics through regulating sympathetic innervation. (2015)
  • Author(s): Ohno M, Nishi K, Hiraoka Y, Niizuma S, Saijo S, Sakamoto J, Chen P-M, Morita Y, Matsuda S, Kita T, Kimura T, Nishi E.
  • Organizer: 第38回日本分子生物学会年会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-01
• [Presentation] ナルディライジンによる交感神経系を介した循環動態の制御 (2015)
  • Author(s): 大野美紀子、平岡義範、松浦博、西清人、西城さやか、坂本二郎、陳博敏、森田雄介、北徹、木村剛、西英一郎
  • Organizer: 第16回日本循環制御医学会
  • Place of Presentation: ウインクあいち
  • Year and Date: 2015-06-05
• [Presentation] Nardilysin controls heart rate through the regulation of sinus node automaticity (2015)
  • Author(s): Ohno M, Nishi K, Saijo S, Sakamoto J, Chen P-M, Morita Y, Makiyama T, Kita T, Matsuura H, Kimura T, Nishi E.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2015-04-24
• [Book] 認知症学会誌 Dementia Japan (2016)
  • Author(s): 大野美紀子 西英一郎
  • Total Pages: 5
  • Publisher: 笹氣出版印刷
• [Remarks] 京都大学大学院医学研究科循環器内科学講座 分子病態学研究グループ
  • URL: http://kyoto-u-cardio.jp/kisokenkyu/sentan-bunshi/