Coronary development is regulated by ATP-dependent SWI/SNF chromatin remodeling component BAF180
Coronary development is regulated by ATP-dependent SWI/SNF chromatin remodeling component BAF180
复制标题
DOI：
10.1016/j.ydbio.2008.04.020
复制
发表时间：
2008-07-15
影响因子：
2.7
通讯作者：
Wang, Zhong
中科院分区：
文献类型：
--
作者：
Huang, Xuling;Gao, Xiaolin;Wang, Zhong
解剖引导心外膜细胞谱系正常发育的分子机制对于理解先天性和成人心血管疾病的病因至关重要。在这项研究中，我们描述了BAF180在冠状动脉发展中的功能，BAF180是atp依赖性SWI/SNF染色质重塑复合体中的一种多溴化蛋白。消融BAF180导致E11.5左右的上皮-间质转化（EMT）受损，心外膜成熟阻滞。三维胶原凝胶分析显示，BAF180突变心外膜细胞确实具有明显的迁移和EMT潜力。因此，突变心脏形成异常的表面结节，不能形成覆盖E14周围整个心室的细小连续的冠状血管丛。PECAM和α - sma染色分析表明，这些结节是由于其内部内皮细胞和平滑肌细胞无法形成冠状血管而导致的缺陷结构。PECAM染色也显示突变心脏的心肌内冠状血管非常少。与此一致的是，定量RT-PCR分析表明，在突变心脏中，与冠状动脉发育至关重要的FGF、TGF和VEGF通路相关的基因表达下调。总之，这些数据首次揭示了BAF180对冠状血管形成至关重要。(c) 2008爱思唯尔公司版权所有。
Dissecting the molecular mechanisms that guide the proper development of epicardial cell lineages is critical for understanding the etiology of both congenital and adult forms of human cardiovascular disease. In this study, we describe the function of BAF180, a polybromo protein in ATP-dependent SWI/SNF chromatin remodeling complexes, in coronary development. Ablation of BAF180 leads to impaired epithelial-to-mesenchymal-transition (EMT) and arrested maturation of epicardium around E11.5. Three-dimensional collagen gel assays revealed that the BAF180 mutant epicardial cells indeed possess significantly compromised migrating and EMT potentials. Consequently, the mutant hearts form abnormal surface nodules and fail to develop the fine and continuous plexus of coronary vessels that cover the entire ventricle around E14. PECAM and alpha-SMA staining assays indicate that these nodules are defective structures resulting from the failure of endothelial and smooth muscle cells within them to form coronary vessels. PECAM staining also reveal that there are very few coronary vessels inside the myocardium of mutant hearts. Consistent with this, quantitative RT-PCR analysis indicate that the expression of genes involved in FGF, TGF, and VEGF pathways essential for coronary development are down-regulated in mutant hearts. Together, these data reveal for the first time that BAF180 is critical for coronary vessel formation. (c) 2008 Elsevier Inc. All rights reserved.