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首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Signaling mechanisms underlying strain-dependent brain natriuretic peptide gene transcription.
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Signaling mechanisms underlying strain-dependent brain natriuretic peptide gene transcription.

机译:应变依赖型脑利钠肽基因转录的信号传导机制。

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Activation of brain natriuretic peptide (BNP) gene promoter activity represents one of the earliest and most reliable markers of ventricular cardiac myocyte hypertrophy. We recently demonstrated that mechanical strain increases immunoreactive BNP secretion, steady-state BNP mRNA levels and BNP gene transcriptional activity in neonatal rat myocyte cultures. We have also shown that strain-dependent BNP gene transcription is critically dependent on the functional integrity of a number of integrins (specfically beta1, beta3, and alpha(v)beta5 integrins) present on the surface of cardiac myocytes. When used alone, each of these antibodies resulted in a significant reduction in strain-dependent activation of a transfected hBNP-luciferase reporter and inhibition of a number of signaling pathways that have been linked to stimulation of this reporter (e.g., extracellular signal regulated kinase and c-Jun amino terminal kinase). The present study shows that combinations of these antibodies resulted in further reductions in hBNP gene promoter activity and inhibition of the relevant signaling cascades. These studies provide further support for the importance of integrin-matrix interactions in promoting strain-dependent changes in cardiac myocyte gene transcription.
机译:脑利钠肽(BNP)基因启动子活性的激活代表心室心肌细胞肥大的最早和最可靠的标志之一。我们最近证明,机械应变增加了新生大鼠心肌细胞培养物中的免疫反应性BNP分泌,稳态BNP mRNA水平和BNP基因转录活性。我们还表明,应变依赖性BNP基因转录严重依赖于存在于心肌细胞表面的许多整合素(特别是beta1,beta3和alpha(v)beta5整合素)的功能完整性。当单独使用时,这些抗体中的每一种都会导致转染的hBNP-荧光素酶报告基因的菌株依赖性激活显着降低,并抑制许多与刺激该报告基因相关的信号通路(例如,细胞外信号调节激酶和c-Jun氨基末端激酶)。本研究表明,这些抗体的组合导致hBNP基因启动子活性进一步降低,并抑制了相关的信号级联反应。这些研究为整合素-基质相互作用在促进心肌细胞基因转录中依赖于应变的变化中的重要性提供了进一步的支持。

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