Factors inducing final cardiomyocyte maturation in newborn mice

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16488
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Shinshu University
• Principal Investigator: KAWAGISHI Hiroyuki 信州大学, 先鋭領域融合研究群バイオメディカル研究所, 助教 (30819082)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 心筋細胞 / 分裂増殖 / gp130 / 新生児

Outline of Final Research Achievements

Mammalian ventricular cardiomyocytes are still premature at birth and continue to differentiate by weaning. Mouse ventricular cardiomyocytes also undergo physiological cell division several times within approximately one week after birth, it is, however, still unclear what roles this proliferation plays in the postnatal cardiac maturation. Here, we examined a role of gp130, a main subunit of receptors for the interleukin-6 family of cytokines in this process. Pharmacological and genetic ablation of gp130 dramatically impaired physiological proliferation of cardiomyocytes in the left ventricle. These mice have the smaller number of the left ventricular cardiomyocytes and indicated significant weak contractility of the left ventricle. Taken together, we found that gp130 played a crucial role in the physiological proliferation of ventricle cardiomyocytes in postnatal developing stage, which is important for the functional development of mammalian heart.

Free Research Field

分子薬理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、哺乳類の生後に起こる心筋細胞の表現型変化について研究を行い、生理的分裂増殖におけるgp130シグナルの役割を明らかにした。近年、成人においても心筋細胞はわずかながら分裂増殖していることが知られており、この分裂増殖能の制御は心筋再生医療における重要な知見であると考えられる。また、乳幼児期の心筋細胞分裂を阻害すると、心機能の低下が引き起こされることを明らかにした。これは、たとえば乳幼児期に抗腫瘍薬治療を受けた患者では心筋細胞の分裂増殖が阻害されることで将来の心機能が低下する（心筋障害）という懸念を示しており、小児がんサバイバーにとって循環器領域のフォローアップの重要性が改めて示された。