Department of Cardiology, Peking University Third Hospital, Beijing 100191, China.
Differentiation. 2013 Jul-Sep;86(1-2):23-9. doi: 10.1016/j.diff.2013.06.007. Epub 2013 Aug 7.
As embryonic stem cells (ESCs) represent an attractive candidate cell source for obtaining cardiomyocytes to be used in cell replacement therapy, it is thus of considerable importance to understand the mechanism by which cardiac differentiation is regulated. In previous studies, we have shown that angiotensin type 1 receptor (AT1R) expressed in cardiomyocytes derived from mouse embryonic stem cells. However, little is known about the role of AT1R in cardiac differentiation, which plays a key role in cardiac physiology and pharmacology. In the present study, we demonstrated that AT1R agonist significantly enhanced cardiac differentiation as determined by increased percentage of beating embryoid bodies and a higher expression level of cardiac markers. On the contrary, AT1R agonist stimulated differentiation was reversed in the presence of AT1R antagonist. In addition, by administering selective inhibitors we found that the effect of AT1R was driven via extracellular-signal regulated kinase, c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase pathways. These findings suggest that AT1R signaling plays a key role in cardiac differentiation of ESCs.
胚胎干细胞（ESCs）作为一种有吸引力的候选细胞来源，可用于获得用于细胞替代治疗的心肌细胞，因此了解心脏分化的调控机制非常重要。在之前的研究中，我们已经表明，在源自小鼠胚胎干细胞的心肌细胞中表达血管紧张素 I 型受体（AT1R）。然而，对于 AT1R 在心脏分化中的作用知之甚少，而心脏分化在心脏生理学和药理学中起着关键作用。在本研究中，我们证明 AT1R 激动剂通过增加搏动胚状体的百分比和提高心脏标志物的表达水平，显著增强了心脏分化。相反，在存在 AT1R 拮抗剂的情况下，AT1R 激动剂刺激的分化被逆转。此外，通过给予选择性抑制剂，我们发现 AT1R 的作用是通过细胞外信号调节激酶、c-Jun NH2-末端激酶和 p38 丝裂原活化蛋白激酶途径驱动的。这些发现表明，AT1R 信号在 ESC 的心脏分化中起着关键作用。
