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
Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Ke Xue Da Dao 100, Zhengzhou, 450001, Henan, China.
Cell Mol Life Sci. 2015 May;72(10):2005-22. doi: 10.1007/s00018-014-1795-9. Epub 2014 Dec 14.
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.
心脏分化的调控对于维持正常的心脏发育和功能至关重要。心脏分化的调控的确切机制仍不明确。在此，我们鉴定出一个GATA - 4靶点——表皮生长因子（EGF），它对心脏发生至关重要，并以剂量和时间依赖的方式调节心脏分化。此外，EGF在诱导P19CL6细胞的心脏分化过程中，与GATA - 4呈现出时间和剂量依赖性的功能相互作用。在生化层面，GATA - 4与信号转导和转录激活因子3（STAT3）形成复合物，以响应EGF刺激结合到EGF启动子上，并协同激活EGF启动子。在功能层面，EGF激活过程中的协同作用导致细胞周期蛋白D1表达的后续激活，这部分解释了GATA - 4/STAT3复合物缺乏额外诱导心脏分化的原因。因此，我们提出了一个心脏分化调控级联涉及GATA - 4、EGF和细胞周期蛋白D1的模型。
