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Flow pattern-dependent endothelial cell responses through transcriptional regulation

机译:通过转录调节流动模式依赖性内皮细胞应答

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摘要

Blood flow provides endothelial cells (ECs) lining the inside of blood vessels with mechanical stimuli as well as humoral stimuli. Fluid shear stress, the frictional force between flowing blood and ECs, is recognized as an essential mechanical cue for vascular growth, remodeling, and homeostasis. ECs differentially respond to distinct flow patterns. High laminar shear flow leads to inhibition of cell cycle progression and stabilizes vessels, whereas low shear flow or disturbed flow leads to increased turnover of ECs and inflammatory responses of ECs prone to atherogenic. These differences of EC responses dependent on flow pattern are mainly ascribed to distinct patterns of gene expression. In this review, we highlight flow pattern-dependent transcriptional regulation in ECs by focusing on KLF2 and NFB, major transcription factors responding to laminar flow and disturbed flow, respectively. Moreover, we introduce roles of a new flow-responsive transcriptional co-regulator, YAP, in blood vessel maintenance and discuss how these transcriptional regulators are spatiotemporally regulated by flow and then regulate EC functions in normal and pathological conditions.
机译:血流为血管内的内皮细胞提供机械刺激和体液刺激。流体剪切应力是流动的血液和内皮细胞之间的摩擦力,被认为是血管生长、重塑和内环境稳定的重要机械信号。ECs对不同的流动模式有不同的响应。高层流剪切流可抑制细胞周期进程并稳定血管,而低剪切流或扰动流可增加内皮细胞的周转,并增加内皮细胞的炎症反应,从而导致动脉粥样硬化。这些依赖于流型的EC反应差异主要归因于不同的基因表达模式。在这篇综述中,我们通过关注KLF2和NFB,分别对层流和扰动流做出反应的主要转录因子,强调了ECs中依赖于流型的转录调控。此外,我们还介绍了一种新的流反应转录共调节因子YAP在血管维护中的作用,并讨论了这些转录调节因子如何在正常和病理条件下受流时空调节,进而调节EC功能。

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