Bone morphogenetic protein-2 acts upstream of myocyte-specific enhancer factor 2a to control embryonic cardiac contractility.
Bone morphogenetic protein-2 acts upstream of myocyte-specific enhancer factor 2a to control embryonic cardiac contractility.
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DOI：
10.1016/j.cardiores.2007.02.007
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发表时间：
2007-05
影响因子：
10.8
通讯作者：
Yue-xiang Wang;Lin-xi Qian;Dong Liu;L. Yao;Qiu Jiang;Zhang Yu;Y. Gui;T. Zhong;Hou-yan Song
中科院分区：
文献类型：
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作者：
Yue-xiang Wang;Lin-xi Qian;Dong Liu;L. Yao;Qiu Jiang;Zhang Yu;Y. Gui;T. Zhong;Hou-yan Song
目的：心肌收缩力作为心脏的一种内在和外在的自我平衡机制受到严格的调节。内在系统的分子基础在很大程度上是未知的。方法：采用RT-PCR、Western blotting、原位分子杂交和体内转基因技术，分析BMP-2和MEF 2A基因在胚胎心肌细胞中的表达情况。分析BMP-2和MEF 2A敲低斑马鱼胚胎的心脏表型。用摄像机记录心脏收缩。透射电镜观察肌原纤维结构。基因表达谱进行定量实时PCR analysis.Results：我们证明，BMP-2和MEF 2A共表达在胚胎和新生心肌细胞。此外，我们提供的证据表明，BMP-2是所需的心脏收缩在体外和在体内，MEF 2A的表达可以激活BMP-2信号在新生心肌细胞。BMP-2参与心脏收缩器官的组装。最后，我们发现，外源性MEF 2A是足以挽救心室收缩力缺陷的情况下，BMP-2 function.Conclusions：在所有的，这些观察表明，BMP-2和MEF 2A是关键组成部分的一个途径，控制心脏心室收缩力，并建议BMP-2-MEF 2A途径可以提供新的机会，治疗心力衰竭。
Objective: Cardiac contractility is regulated tightly as an extrinsic and intrinsic homeostatic mechanism to the heart. The molecular basis of the intrinsic system is largely unknown. Here, we test the hypothesis thatbone morphogenetic protein-2(BMP-2) mediates embryonic cardiac contractility upstream ofmyocyte-specific enhancer factor 2A(MEF2A).Methods: The BMP-2 and MEF2A expression pattern was analyzed by RT-PCR, Western blotting, whole-mountin situhybridization, and anin vivotransgenic approach. The cardiac phenotype of BMP-2 and MEF2A knock-down zebrafish embryos was analysed. Cardiac contractions were recorded with a video camera. Myofibrillar organization was observed with transmission electron microscopy. Gene expression profiles were performed by quantitative real-time PCR analysis.Results: We demonstrate that BMP-2 and MEF2A are co-expressed in embryonic and neonatal cardiac myocytes. Furthermore, we provide evidence that BMP-2 is required for cardiac contractilityin vitroandin vivoand that MEF2A expression can be activated by BMP-2 signaling in neonatal cardiomyocytes. BMP-2 is involved in the assembly of the cardiac contractile apparatus. Finally, we find that exogenous MEF2A is sufficient to rescue ventricular contractility defects in the absence of BMP-2 function.Conclusions: In all, these observations indicate that BMP-2 and MEF2A are key components of a pathway that controls the cardiac ventricular contractility and suggest that the BMP2-MEF2A pathway can offer new opportunities for the treatment of heart failure.