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首页> 外文期刊>Life sciences >Mitogen-activated protein kinase activation induces corticotrophin-releasing hormone gene expression in human placenta.
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Mitogen-activated protein kinase activation induces corticotrophin-releasing hormone gene expression in human placenta.

机译：丝裂原活化的蛋白激酶活化诱导人胎盘中促肾上腺皮质激素释放激素基因的表达。

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摘要

Corticotropin-releasing hormone (CRH) gene expression in human placental cells is induced by activation of the cyclic AMP and protein kinase C signal transduction pathways, but the role of the mitogen-activated kinase (MAPK) pathway is unknown. In this study, we showed that the MAPK inhibitor, PD098059, causes a dose-dependent inhibition of placental CRH gene expression. In contrast, overexpression of RAF in human choriocarcinoma JEG cells stimulates CRH promoter activity by 15-fold, and the stimulation is inhibited by 65% by co-transfection of the cells with a plasmid expressing a RAF dominantegative protein. The stimulation by RAF was completely abolished by mutation of the cyclic AMP response element (CRE) in the proximal region of the CRH promoter. Taken together, these results strongly suggest that the MAPK signal transduction pathway plays a pivotal role in the regulation of CRH gene expression in human placenta, and that the CRE binding site in the proximal CRH promoter acts as a point of convergence for different signal transduction pathways in the regulation of CRH gene expression in placenta cells.
机译：促性腺激素释放激素（CRH）基因在人胎盘细胞中的表达是由环状AMP和蛋白激酶C信号转导途径的激活诱导的，但是促分裂原激活激酶（MAPK）的作用尚不清楚。在这项研究中，我们表明MAPK抑制剂PD098059引起胎盘CRH基因表达的剂量依赖性抑制。相反，RAF在人绒癌组织JEG细胞中的过表达将CRH启动子活性刺激了15倍，并且通过与表达RAF显性/负性蛋白的质粒共转染细胞，刺激被65％抑制。 RAF的刺激被CRH启动子近端区域中的环状AMP反应元件（CRE）突变完全消除了。综上所述，这些结果强烈表明，MAPK信号转导途径在人类胎盘中CRH基因表达的调节中起着关键作用，并且近端CRH启动子中的CRE结合位点充当了不同信号转导途径的汇合点。调节胎盘细胞中CRH基因的表达

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