Molecular Mechanism and Hemodynamic Function in the Outflow Tract of Heart

心脏流出道的分子机制和血流动力学功能

• 批准号: 12470172
• 负责人: NAKAZAWA Makoto
• 金额: $ 8万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470172/
• 关键词: heart; the outflow tract; jumonji; mouse embryo; chick embryo; development; the cardiac neural crest; Jumonji遺伝子; Jumonji

The recessive mutant mouse Jumonji, obtained by a gene trap strategy, shows cardiac defects. Myocytes in the ventricular trabeculae show hyperproliferation suggesting that Jumonji gene downregulates cell growth of the cardiac myocytes. Jumonj - overexpressing mice shows repression of cyclin D1 expression in the heart. We found that Jumonj protein binds to a region in the cyclin D1 promoter and represses the promoter activity. Cyclin D1-overexpressing mice shows same abnormalities observed in the heart of Jumonj mutant mice. These results showed that Jumonj gene downregulates cell growth of the cardiac myocytes by repressing the expression of cyclin D1 directly. Furthermore, cyclin D1 is necessary for th e arrest of cardiac proliferation. Ablation of the premigrated cardiac neural crest from chick embryos induces trucus areteriosus in heart. Resulting from the ablation and transplantation experiments of the cardiac neural crest in chick embryos shows that the cardiac neural crest may regulate proliferation and cell death of myocardium.

通过基因陷阱策略获得的隐性突变小鼠Jumonji显示了心脏缺陷。心室小梁中的心肌细胞表现出过度增殖，这表明Jumonji基因下调了心肌细胞的细胞生长。 Jumonj-过表达的小鼠显示了心脏中细胞周期蛋白D1表达的抑制。我们发现Jumonj蛋白与细胞周期蛋白D1启动子中的区域结合并抑制启动子活性。在Jumonj突变小鼠的心脏中观察到的过表达Cyclin D1的小鼠表现出相同的异常。这些结果表明，Jumonj基因通过直接抑制细胞周期蛋白D1的表达来下调心肌细胞的细胞生长。此外，细胞周期蛋白D1对于逮捕心脏增殖是必需的。从雏鸡胚胎中消融的心脏神经rest消融会引起心脏的trucus areteriosus。由雏鸡胚胎中心脏神经rest的消融和移植实验引起的，表明心脏神经rest可能调节心肌的增殖和细胞死亡。

项目成果

Sugimura H, Miyagawa-Tomita S, Nakazawa M: "Effect of the cardiac neural crest for the coronary angiogenesis and/or vasculogenesis"Weinstein Cardiovasc Meeting, Salt Lake, Utah, USA. (2002)

Sugimura H、Miyakawa-Tomita S、Nakazawa M：“心脏神经嵴对冠状动脉血管生成和/或血管发生的影响”Weinstein Cardiovasc Meeting，美国犹他州盐湖城。

Osada, T., Watanabe, G., Sasaki, Y., Takeuchi, T.: "Puromycin-sensitive aminopeptidase is essential for maternal recognition of pregnancy in mice"Molecular Endocrinology. 15. 882-893 (2001)

Osada, T.、Watanabe, G.、Sasaki, Y.、Takeuchi, T.：“嘌呤霉素敏感氨肽酶对于母体识别小鼠妊娠至关重要”分子内分泌学。

Suzuki A, Miyagawa-Tomita S, Nakazawa M, Yutani C: "Remodeling of coronary artery lesions due to Kawasaki Disease"Jpn Heart J. 41(3). 245-256 (2000)

Suzuki A、Miyakawa-Tomita S、Nakazawa M、Yutani C：“川崎病引起的冠状动脉损伤的重塑”Jpn Heart J. 41(3)。

Toyoda, M., Kojima, M., Takeuchi, T.: "Jumonji proteinis a nuclear protein that participates in the negative regulation of cell growth"Biochem. Biophys. Res. Commun. 274. 332-336 (2000)

Toyoda, M.、Kojima, M.、Takeuchi, T.：“Jumonji 蛋白是一种参与细胞生长负调节的核蛋白”Biochem。

Kitajima S, Takagi A, Miyagawa-Tomita S, Inoue T, Saga Y: "Analysis of cell lineage in cardiogenesis indicated by expression of transcription factor Mesp1."24th Mol Biol Society Jpn, Yokohama, Japan. 4-52S (2001)

Kitajima S、Takagi A、Miyakawa-Tomita S、Inoue T、Saga Y：“通过转录因子 Mesp1 的表达来分析心脏发生中的细胞谱系”。第 24 届 Mol Biol Society Jpn，日本横滨。