2020 Fiscal Year Final Research Report
Identification of factors promoting final differentiation of cardiac myocytes after birth
| Project/Area Number |
18K06870
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 48020:Physiology-related
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| Research Institution | Shinshu University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 新生児 / 心臓 / 細胞分裂 / 分化 / インターロイキン6 / gp130 / 腫瘍心臓病学 / 小児がん |
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| Outline of Final Research Achievements |
Different from the widely accepted belief, cardiac myocytes of mammals including human are not ‘terminally differentiated’ at birth. They are still both structurally and functionally too immature to ensure their robust aerobic extrauterine life. In the case of mice, for instance, they cease cell division around 1 week old, and then, start to differentiate to the mature level by approximately one month. Interestingly, we here found for the first time that the most important driver of the initial cell division in the left ventricle is the interleukin 6/gp130 signaling system, and that it is necessary for establishing the normal myocyte number, wall thickness, and the contractility of the left ventricle. Thus, this pathway might be druggable in the regenerative medicine for the late-onset left ventricular dysfunction sometimes manifested in pediatric cancer survivors.
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| Free Research Field |
薬理学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の学術的意義は，①哺乳類の出生後早期の一過性心筋細胞分裂が，成長後の心臓の形態・機能形成に重要であること，②それが主としてインターロイキン-6／gp130シグナルにより駆動されることを見出したことである。近年，ヒトの心筋細胞も胎児期・新生児期の後も，わずかながら継続的に分裂していることが知られ，再生療法への応用が期待されている。また近年，小児がん治療を受けた小児が，永年後心機能低下生じることがあることが知られ，Oncocardilogy的課題となっている。本研究は，小児心臓病治療にサイトカイン／gp130系が応用できる可能性をはじめて示した社会的意義がある。
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