Elucidation of ErbB receptor signaling pathway for cardiac regenerative medicine

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kansai Medical University
• Principal Investigator: HIRAI Maretoshi 関西医科大学, 医学部, 講師 (60422929)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 心筋細胞 / ErbB受容体 / 細胞周期活性 / 心筋再生

Outline of Final Research Achievements

Tyrosine kinase receptors have attracted attention as receptors with potent proliferative activity and as targets for cardiac regeneration therapy. In this study, we independently generated and analyzed cardiomyocyte-specific ErbB2 overexpressing mice and cardiomyocyte-specific ErbB4 overexpressing mice, and have approached their molecular function. Although ErbB2/4 receptors have been considered to activate the same common signaling pathway, our mice exhibited a completely different phenotype, with enhanced cardiac function for ErbB2 and severely impaired cardiac function for ErbB4. In addition, contrary to conventional idea, ErbB2 overexpression did not enhance cardiomyocyte cell cycle activity, but was found to be a factor required for cardiomyocyte alignment.

Free Research Field

循環器内科学、薬理学、分子生物学、発生生物学、生物物理学

Academic Significance and Societal Importance of the Research Achievements

本研究により心筋再生治療の有望な候補と考えられてきた、ErbBシグナル経路の本質に迫ることができた。従来はErbB2/4受容体は同じシグナル経路を活性化することが考えられてきたが、それぞれの過剰発現マウスはまったく異なる表現型を呈した。そのため異なる下流シグナル経路を活性化すると考えられる。心筋再生治療のターゲットとして、より繊細なコントロールを必要とすることが判明した。そのため本研究による知見は、将来の心筋再生治療の考え方に変革をもたらす可能性がある。