Transcriptional and post-translation regulation of the Tie1 receptor by fluid shear stress changes in vascular endothelial cells
Transcriptional and post-translation regulation of the Tie1 receptor by fluid shear stress changes in vascular endothelial cells
复制标题
DOI：
10.1096/fj.02-1151fje
复制
发表时间：
2003-09-01
期刊：
影响因子：
4.8
通讯作者：
Resnick, N
中科院分区：
文献类型：
--
作者：
Chen-Konak, L;Guetta-Shubin, Y;Resnick, N
由血流引起的血管内皮和血流动力学力（更具体地说，流体剪切应力）之间的相互作用在血管重塑和新血管形成过程中起着重要作用，这一过程被称为动脉生成。Tiel是一种罕见的酪氨酸激酶受体，几乎只在内皮细胞中表达，是正常血管发育和维持所必需的。本研究表明，在受剪切应力影响的内皮细胞中，Tiel的表达会迅速下调，剪切应力变化对其表达的影响更大。这种下调伴随着Tiel的快速切割和被切割的Tiel 45kda内结构域与Tie2的结合。Tiel的快速裂解随后是响应剪切应力的转录下调。Tiel启动子的活性受到剪切应力和肿瘤坏死因子a的抑制。剪切应力诱导的Tiel转录抑制是由一个负剪切应力响应元件介导的，该元件位于启动子内250个区域。剪应力变化对Tiel的快速下调及其与Tie2的快速结合可能是内皮细胞不稳定以启动血管重构过程所必需的。
The interaction between the vascular endothelium and hemodynamic forces (and more specifically, fluid shear stress), induced by the flow of blood, plays a major role in vascular remodeling and in new blood vessels formation via a process termed arteriogenesis. Tiel is an orphan tyrosine kinase receptor expressed almost exclusively in endothelial cells and is required for normal vascular development and maintenance. The present study demonstrates that Tiel expression is rapidly down-regulated in endothelial cells exposed to shear stress, and more so to shear stress changes. This down-regulation is accompanied by a rapid cleavage of Tiel and binding of the cleaved Tiel 45 kDa endodomain to Tie2. The rapid cleavage of Tiel is followed by a transcriptional down-regulation in response to shear stress. The activity of the Tiel promoter is suppressed by shear stress and by tumor necrosis factor a,. Shear stress-induced transcriptional suppression of Tiel is mediated by a negative shear stress response element, localized in a region of 250 by within the promoter. The rapid down-regulation of Tiel by shear stress changes and its rapid binding to Tie2 may be required for destabilization of endothelial cells in order to initiate the process of vascular restructuring.