EGF is required for cardiac differentiation of P19CL6 cells through interaction with GATA-4 in a time- and dose-dependent manner

EGF is required for cardiac differentiation of P19CL6 cells through interaction with GATA-4 in a time- and dose-dependent manner
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P19CL6 细胞的心脏分化需要 EGF 通过与 GATA-4 以时间和剂量依赖性方式相互作用

DOI:
10.1007/s00018-014-1795-9
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发表时间:
2014-12
影响因子:
8
通讯作者:
Zang Ming-Xi
Zang Ming-Xi
中科院分区:
生物学1区
文献类型:
--
作者:
Ma Cai-Xia;Song Yang-Liu;Xiao Liyun;Xue Li-Xiang;Li Wen-Juan;Laforest Brigitte;Komati Hiba;Wang Wei-Ping;Jia Zhu-Qing;Zhou Chun-Yan;Zou Yunzeng;Nemer Mona;Zhang Shan-Feng;Bai Xiaowen;Wu Huijian;Zang Ming-Xi

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心脏分化的调节是维持心脏正常发育和功能的关键。心脏分化被调控的确切机制仍不确定。在这里,我们已经确定了一个GATA-4靶点,EGF,它是心脏发生所必需的,并以剂量和时间依赖的方式调节心脏分化。此外,EGF与GATA-4以时间和剂量依赖的方式在诱导P19CL6细胞分化方面显示出功能上的相互作用。在生物化学方面,GATA-4与STAT3形成一个复合体,以响应EGF的刺激而与EGF启动子结合并协同激活EGF启动子。在功能上,EGF激活过程中的协同作用导致细胞周期蛋白D1的表达随后被激活,这在一定程度上解释了GATA-4/STAT3复合体没有额外诱导心脏分化。因此,我们提出了一个模型,在该模型中,心脏分化的调节级联涉及GATA-4、EGF和细胞周期蛋白D1。
The regulation of cardiac differentiation is critical for maintaining normal cardiac development and function. The precise mechanisms whereby cardiac differentiation is regulated remain uncertain. Here, we have identified a GATA-4 target, EGF, which is essential for cardiogenesis and regulates cardiac differentiation in a dose- and time-dependent manner. Moreover, EGF demonstrates functional interaction with GATA-4 in inducing the cardiac differentiation of P19CL6 cells in a time- and dose-dependent manner. Biochemically, GATA-4 forms a complex with STAT3 to bind to the EGF promoter in response to EGF stimulation and cooperatively activate the EGF promoter. Functionally, the cooperation during EGF activation results in the subsequent activation of cyclin D1 expression, which partly accounts for the lack of additional induction of cardiac differentiation by the GATA-4/STAT3 complex. Thus, we propose a model in which the regulatory cascade of cardiac differentiation involves GATA-4, EGF, and cyclin D1.
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