Effects of Regulator of G Protein Signaling 19 (RGS19) on Heart Development and Function
Effects of Regulator of G Protein Signaling 19 (RGS19) on Heart Development and Function
复制标题
DOI：
10.1074/jbc.m109.073718
复制
发表时间：
2010-09-10
影响因子：
4.8
通讯作者：
Ryoo, Zae Young
中科院分区：
文献类型：
--
作者：
Ji, Young Rae;Kim, Myoung Ok;Ryoo, Zae Young
Wnt/Wg基因在多种生物的发育中起着至关重要的作用。例如，Wnt/ β -连环蛋白信号促进小鼠心脏形成和心肌细胞分化。先前的研究表明，RGS19 ((r) under bar的(G) under bar蛋白（s) under bar信号传导（19）under bar）的调节因子(r)具有GTPase活性的G α亚基，通过G α (o)的失活来抑制Wnt/ β -catenin信号。本研究观察了RGS19对小鼠心脏发育的影响。在RGS19过表达的P19畸胎癌细胞中，RGS19通过阻断Wnt信号抑制心肌细胞分化。此外，Wnt靶向的几个基因被下调。在体内研究中，我们培育了RGS19过表达转基因（RGS19 TG）小鼠。在这些转基因小鼠中，在胚胎发育阶段观察到室间隔缺陷和薄壁心室，并且心脏发生相关基因BMP4和Mef2C的表达显著降低。RGS19 TG小鼠表现出心衰标志物脑利钠肽和β - mhc表达水平升高，细胞增殖增加，心电图分析显示心室复极异常。这些数据为RGS19影响心脏发育并对心脏功能产生负面影响提供了体外和体内证据。
Wnt/Wg genes play a critical role in the development of various organisms. For example, the Wnt/beta-catenin signal promotes heart formation and cardiomyocyte differentiation in mice. Previous studies have shown that RGS19 ((r) under bar egulator of (G) under bar protein (s) under bar ignaling (19) under bar), which has G alpha subunits with GTPase activity, inhibits the Wnt/beta-catenin signal through inactivation of G alpha(o). In the present study, the effects of RGS19 on mouse cardiac development were observed. In P19 teratocarcinoma cells with RGS19 overexpression, RGS19 inhibited cardiomyocyte differentiation by blocking the Wnt signal. Additionally, several genes targeted by Wnt were down-regulated. For the in vivo study, we generated RGS19-overexpressing transgenic (RGS19 TG) mice. In these transgenic mice, septal defects and thin-walled ventricles were observed during the embryonic phase of development, and the expression of cardiogenesis-related genes, BMP4 and Mef2C, was reduced significantly. RGS19 TG mice showed increased expression levels of brain natriuretic peptide and beta-MHC, which are markers of heart failure, increase of cell proliferation, and electrocardiogram analysis shows abnormal ventricle repolarization. These data provide in vitro and in vivo evidence that RGS19 influenced cardiac development and had negative effects on heart function.