Induction of proliferation of mature cardiac myocytes through ErbB receptor signalling pathway

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09586
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kansai Medical University
• Principal Investigator: HIRAI Maretoshi 関西医科大学, 医学部, 講師 (60422929)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 心筋細胞 / 増殖 / ErbB受容体 / 細胞周期

Outline of Final Research Achievements

Among a couple of ErbB receptor families, ErbB2 and ErbB4 receptors play an important function to maintain homeostasis of the heart. In this project, we examined if overexpression of either ErbB2 or ErbB4 receptor could induce proliferation of cardiac myocytes, thus examined the possibility of future novel regenerative therapy for heart diseases. It is broadly considered that both ErbB2 and ErbB4 activate the same signaling pathway by configuring heterodimer or homodimer. However, the phenotype of ErbB2 overexpressed heart was shown to be in keen contrast to that of ErbB4 overexpressed heart. Thus, to regulate and induce proliferation of cardiac myocytes in adult, we need different approach from the idea people currently assume.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

心筋細胞は生後細胞周期の休止期に入りその後増殖することはない。そのため心筋梗塞で心筋細胞が失われると心機能障害をきたし心不全を発症してしまう。本研究ではマウスで成長因子受容体シグナルを活性化することにより、成熟心筋細胞の増殖を誘導しうるかどうかを明らかにすることを目的とした。本研究の結果、心筋細胞で成長因子受容体を過剰発現させ、その細胞を1細胞レベルで直接可視化できるマウスの作製に成功した。今後、このマウスを用いて、成熟心筋細胞の増殖を誘導することが可能であれば、梗塞後心不全に対する新規治療の開発への展望が開けるだろう。