先天性心脏病中的骨形态发生蛋白信号传导：新进展与未来方向
BMP signaling in congenital heart disease: new developments and future directions.
作者信息
Wang Jun, Greene Stephanie B, Martin James F
机构信息
Institute of Biosciences and Technology, Texas A&M System Health Science Center, 2121 W. Holcombe Blvd., Houston, TX 77030, USA.
出版信息
Birth Defects Res A Clin Mol Teratol. 2011 Jun;91(6):441-8. doi: 10.1002/bdra.20785. Epub 2011 Mar 7.
Abstract
Congenital heart malformations are the most common of all congenital human birth anomalies. During the past decade, research with zebrafish, chick, and mouse models have elucidated many fundamental genetic pathways that govern early cardiac patterning and differentiation. This review highlights the roles of the bone morphogenetic protein (BMP) signaling pathway in cardiogenesis and how defective BMP signals can disrupt the intricate steps of cardiac formation and cause congenital heart defects.
摘要
先天性心脏畸形是人类所有先天性出生缺陷中最常见的。在过去十年中，对斑马鱼、鸡和小鼠模型的研究阐明了许多控制早期心脏模式形成和分化的基本遗传途径。本综述重点介绍了骨形态发生蛋白（BMP）信号通路在心脏发生中的作用，以及有缺陷的BMP信号如何破坏心脏形成的复杂步骤并导致先天性心脏缺陷。
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本文引用的文献
1
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Dev Cell. 2010 Dec 14;19(6):903-12. doi: 10.1016/j.devcel.2010.10.022.
2
Integration of a Notch-dependent mesenchymal gene program and Bmp2-driven cell invasiveness regulates murine cardiac valve formation.Notch 依赖性间充质基因程序与 Bmp2 驱动的细胞侵袭性的整合调节小鼠心脏瓣膜形成。
J Clin Invest. 2010 Oct;120(10):3493-507. doi: 10.1172/JCI42666. Epub 2010 Sep 20.
3
Myocardial deletion of Smad4 using a novel α skeletal muscle actin Cre recombinase transgenic mouse causes misalignment of the cardiac outflow tract.利用新型α 骨骼肌肌动蛋白 Cre 重组酶转基因小鼠对心肌 Smad4 的缺失导致心脏流出道的错位。
Int J Biol Sci. 2010 Sep 20;6(6):546-55. doi: 10.7150/ijbs.6.546.
4
The FGF-BMP signaling axis regulates outflow tract valve primordium formation by promoting cushion neural crest cell differentiation.FGF-BMP 信号轴通过促进垫状神经嵴细胞分化来调节流出道瓣膜原基的形成。
Circ Res. 2010 Nov 12;107(10):1209-19. doi: 10.1161/CIRCRESAHA.110.225318. Epub 2010 Sep 16.
5
BMP signals promote proepicardial protrusion necessary for recruitment of coronary vessel and epicardial progenitors to the heart.BMP 信号促进心外膜突起，这对于招募冠状血管和心外膜祖细胞到心脏是必需的。
Dev Cell. 2010 Aug 17;19(2):307-16. doi: 10.1016/j.devcel.2010.07.017.
6
Smad proteins bind a conserved RNA sequence to promote microRNA maturation by Drosha.Smad 蛋白结合保守的 RNA 序列，通过 Drosha 促进 microRNA 的成熟。
Mol Cell. 2010 Aug 13;39(3):373-84. doi: 10.1016/j.molcel.2010.07.011.
7
The BMP pathway acts to directly regulate Tbx20 in the developing heart.BMP 通路可直接调节心脏发育过程中的 Tbx20。
Development. 2010 Jun;137(11):1919-29. doi: 10.1242/dev.043588.
8
Tbx5 and Bmp signaling are essential for proepicardium specification in zebrafish.Tbx5 和 Bmp 信号对于斑马鱼前心外膜的特化是必不可少的。
Circ Res. 2010 Jun 25;106(12):1818-28. doi: 10.1161/CIRCRESAHA.110.217950. Epub 2010 Apr 22.
9
Retinoic acid regulates differentiation of the secondary heart field and TGFbeta-mediated outflow tract septation.视黄酸调节次级心脏场的分化和 TGFβ 介导的流出道分隔。
Dev Cell. 2010 Mar 16;18(3):480-5. doi: 10.1016/j.devcel.2009.12.019.
10
T-box 2, a mediator of Bmp-Smad signaling, induced hyaluronan synthase 2 and Tgfbeta2 expression and endocardial cushion formation.T盒蛋白2是骨形态发生蛋白- Smad信号通路的一种介质，可诱导透明质酸合酶2和转化生长因子β2的表达以及心内膜垫的形成。
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