Epithelial Splicing Regulatory Protein 1 (ESRP1) is a new regulator of stomach smooth muscle development and plasticity.
Epithelial Splicing Regulatory Protein 1 (ESRP1) is a new regulator of stomach smooth muscle development and plasticity.
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DOI：
10.1016/j.ydbio.2016.04.015
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发表时间：
2016-06
影响因子：
2.7
通讯作者：
Sébastien Sagnol;S. Marchal;Yinshan Yang;F. Allemand;P. de Santa Barbara
中科院分区：
文献类型：
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作者：
Sébastien Sagnol;S. Marchal;Yinshan Yang;F. Allemand;P. de Santa Barbara
在脊椎动物中，胃平滑肌发育是一个复杂的过程，涉及不同信号通路的紧密转录或转录后调控。在这里，我们确定了RNA结合蛋白上皮剪接调节蛋白1（ESRP1）作为发展和未分化的胃间质的早期标志物。利用功能获得方法，我们发现在鸡胚胎中，ESRP 1的持续表达损害胃平滑肌细胞（SMC）分化和FGFR 2剪接模式。ESRP1在原代分化的胃平滑肌细胞中的过表达诱导了它们的去分化，促进了特异性FGFR2b的剪接，并降低了FGFR2c依赖的活性。此外，ESRP 1和RBPMS 2（另一种调节SMC可塑性和骨形态发生蛋白（BMP）通路抑制的RNA结合蛋白）的共表达协同促进SMC去分化。最后，我们还证明了ESRP 1与RBPMS 2相互作用，RBPMS 2介导的SMC去分化需要ESRP 1。总之，这些结果表明ESRP 1也在未分化的胃间充质中表达，并证明其在SMC发育和可塑性中的作用。
In vertebrates, stomach smooth muscle development is a complex process that involves the tight transcriptional or post-transcriptional regulation of different signalling pathways. Here, we identified the RNA-binding protein Epithelial Splicing Regulatory Protein 1 (ESRP1) as an early marker of developing and undifferentiated stomach mesenchyme. Using a gain-of-function approach, we found that in chicken embryos, sustained expression ofESRP1impairs stomach smooth muscle cell (SMC) differentiation andFGFR2splicing profile. ESRP1 overexpression in primary differentiated stomach SMCs induced their dedifferentiation, promoted specific-FGFR2bsplicing and decreased FGFR2c-dependent activity. Moreover, co-expression of ESRP1 and RBPMS2, another RNA-binding protein that regulates SMC plasticity and Bone Morphogenetic Protein (BMP) pathway inhibition, synergistically promoted SMC dedifferentiation. Finally, we also demonstrated that ESRP1 interacts with RBPMS2 and that RBPMS2-mediated SMC dedifferentiation requires ESRP1. Altogether, these results show that ESRP1 is expressed also in undifferentiated stomach mesenchyme and demonstrate its role in SMC development and plasticity.