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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >T-box 2, a mediator of Bmp-Smad signaling, induced hyaluronan synthase 2 and Tgfβ2 expression and endocardial cushion formation
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T-box 2, a mediator of Bmp-Smad signaling, induced hyaluronan synthase 2 and Tgfβ2 expression and endocardial cushion formation

机译:T-box 2是Bmp-Smad信号的介导因子,可诱导透明质酸合酶2和Tgfβ2的表达以及心内膜​​的形成

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摘要

During early heart development, Tbx2 gene expression is initiated in the cardiac crescent and then becomes restricted to the outflow tract and the atrioventricular region. We identified a Tbx2 regulatory region, enriched in multiple Smad sites, sufficient to reproduce Tbx2 expression patterns overlapping Bmp2 and Bmp4 gene activity in the heart. The role of Tbx2 in cardiogenesis was analyzed by using Cre-LoxP activated Tbx2 transgenic misexpression in chamber myocardium. Ventricular Tbx2 misexpression exhibited an abnormally narrow chamber lumen owing to the expansion of Hyaluronan synthase 2 expression in the ECM or cardiac jelly and the appearance of the endocardial cushions (ECs). Excessive Tbx2 also induced Tgfβ2, which coincided with the outgrowth epithelial-mesenchymal transformed cells in ventricular and atrial tissues modifying cardiomyocyte identity from chamber type to non-chamber type. Tbx2, a central intermediary of Bmp-Smad signaling, has a central part in directing Has2 and Tgfβ2 expression, facilitating EC formation.
机译:在早期心脏发育过程中,Tbx2基因表达在心脏新月开始,然后被限制在流出道和房室区域。我们确定了一个Tbx2调节区,富含多个Smad位点,足以在心脏中重现与Bmp2和Bmp4基因活性重叠的Tbx2表达模式。通过使用房室心肌中Cre-LoxP激活的Tbx2转基因错误表达来分析Tbx2在心脏发生中的作用。由于透明质酸合酶2在ECM或cardiac胶中的表达增加以及心内膜​​垫(ECs)的出现,心室Tbx2的错误表达表现出异常狭窄的腔腔。过量的Tbx2也会诱导Tgfβ2,这与心室和心房组织中的上皮间质转化细胞的生长相吻合,从而将心肌细胞的身份从室型转变为非室型。 Tbx2是Bmp-Smad信号传导的核心中介,在指导Has2和Tgfβ2表达,促进EC形成方面具有核心作用。

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