2022 Fiscal Year Final Research Report
Hippo-Yap contributes to cardiomyocyte proliferation in the fetal rat heart with antenatal glucocorticoid administration.
| Project/Area Number |
20K08500
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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 53020:Cardiology-related
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
Matsumoto Naoki 聖マリアンナ医科大学, 医学部, 教授 (80239110)
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| Co-Investigator(Kenkyū-buntansha) |
武半 優子 聖マリアンナ医科大学, 医学部, 准教授 (50367348)
小林 司 聖マリアンナ医科大学, 医学部, 研究技術員 (20822589)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 出生前グルココルチコイド療法 / Hippo-Yap / 心筋細胞 / 胎仔 |
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| Outline of Final Research Achievements |
Although cardiomyocytes can proliferate in the fetal heart, this ability is lost after birth. It is almost impossible for the adult heart to regenerate after injury due to myocardial infarction. The transcriptional co-activator Yes-associated protein (Yap) is required for cardiomyocyte proliferation during the newborn stage. We investigated where Yap activation has occurred in the fetal heart and whether antenatal GC administration affects Yap on cardiomyocyte proliferation. The cell proliferation in the epicardium was greater than that in the endocardium and myocardium in the fetuses. Furthermore, antenatal GC administration promoted cell proliferation. Our results suggested that both cell cycle progression and Yap activation are among the mechanisms involved in fetal cardiomyocyte proliferation in the epicardium Understanding the proliferative mechanisms of fetal heart might be applicable to regenerative therapeutic strategies.
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| Free Research Field |
循環器学
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| Academic Significance and Societal Importance of the Research Achievements |
胎児から新生児期の心筋は、細胞増殖能を有し、成人ではその能力は消失する。胎児期の心筋細胞増殖機構を解明し、胎児期の能力を成人心筋に誘導できれば心筋梗塞などの心筋修復に応用できると考えた。胎児～新生児期の心筋細胞増殖に関与するHippo-Yap経路の機能に着目し、ラット胎仔心筋での発現と、出生前グルココルチコイド（GC）投与後の胎仔での影響を検討した。胎仔および新生仔期の心筋細胞におけるYapの活性化は心筋細胞増殖能に重要な役割を担っていることを明らかにし、GC投与でもその能力が増強することを確認した。これらの機構が、成人心筋に誘導することが可能になれば心筋細胞修復に利用できると考える。
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