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首页> 外文期刊>Cellular Signalling >Cross-talk of SFRP4, integrin alpha 1 beta 1, and Notch1 inhibits cardiac differentiation of P19CL6 cells
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Cross-talk of SFRP4, integrin alpha 1 beta 1, and Notch1 inhibits cardiac differentiation of P19CL6 cells

机译：SFRP4，整合素α1beta 1和Notch1的相互干扰抑制P19CL6细胞的心脏分化

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摘要

Signaling pathways play an important role in cardiogenesis. Secreted frizzled-related protein 4 (SFRP4), a member of the Wnt family, contributes to adipogenesis and tumorigenesis. However, how SFRP4 participates in cardiogenesis and the detailed molecular mechanisms involved have not been elucidated. The aim of this work was to determine cross-talk between SFRP4, integrin alpha 1 beta 1, and Notch1 during cardiac differentiation of P19CL6 cells. Using a well-established in vitro P19CL6 cell cardiomyocyte differentiation system, we found that SFRP4 inhibited P19CL6 cell cardiac differentiation via SFRP4 overexpression or knockdown. In addition, the SFRP4 overexpression augmented Notch1 and HES1 production. Further investigation demonstrated that SFRP4 bound to integrin alpha 1 beta 1 to activate the focal adhesion kinase (FAK) pathway and that phosphorylated FAK Y397 (p-FAK Y397) aided Notch intracellular domain 1 (NICD1) nuclear translocation to form a p-FAK Y397-NICD1 complex that activated the Hest promoter. Taken together, the cross-talk between SFRP4, integrin alpha 1 beta 1, and Notch1 suppresses the cardiac differentiation of P19CL6 cells. (C) 2016 The Authors. Published by Elsevier Inc.
机译：信号通路在心脏发生中起重要作用。分泌的卷曲相关蛋白4（SFRP4）是Wnt家族的成员，有助于脂肪形成和肿瘤发生。但是，尚未阐明SFRP4如何参与心脏发生以及涉及的详细分子机制。这项工作的目的是确定在P19CL6细胞的心脏分化过程中SFRP4，整联蛋白alpha 1 beta 1和Notch1之间的串扰。使用完善的体外P19CL6细胞心肌分化系统，我们发现SFRP4通过SFRP4的过表达或敲低抑制P19CL6细胞的心脏分化。此外，SFRP4过表达增加了Notch1和HES1的产量。进一步的研究表明，SFRP4与整联蛋白alpha 1 beta 1结合以激活粘着斑激酶（FAK）途径，而磷酸化的FAK Y397（p-FAK Y397）辅助Notch细胞内结构域1（NICD1）核易位形成p-FAK Y397 -NICD1复合物，可激活Hest启动子。两者合计，SFRP4，整合素α1 beta 1和Notch1之间的串扰抑制了P19CL6细胞的心脏分化。 （C）2016作者。由Elsevier Inc.发布

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