Apelin receptor signaling: a novel mechanism of endothelial cell polarization
Apelin receptor signaling: a novel mechanism of endothelial cell polarization
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Apelin 受体信号传导：内皮细胞极化的新机制
DOI：
10.1093/abbs/gmw108
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发表时间：
2016
影响因子：
3.7
通讯作者：
Chen Linxi
中科院分区：
文献类型：
--
作者：
Zhao Hong;Yao Pingbo;Li Lanfang;Chen Linxi
细胞极化对于许多类型的细胞是常见的，例如血管内皮细胞（EC）、巨噬细胞和上皮细胞[1]。单个单元具有相对的侧面，并且连接相对侧面的假想轴的方向高度协调。极化轴的这种协调对于器官的功能至关重要，称为平面细胞极性（PCP）[2]。当细胞器、细胞骨架和/或粘附复合体沿轴沿着单向排列时，就会发生这种情况。内皮细胞连续暴露于剪切应力，它们直接表现出深刻的形态学适应，如平面细胞极化，伸长和微管排列。此外，细胞连接的状态和细胞骨架的动态重排对于建立流动诱导的EC极化是重要的，这是维持血管稳态的重要决定因素。EC在流动方向上的对齐需要对机械剪切应力的敏感性以及这些刺激转化为生化信号，其介导功能变化和细胞骨架重塑[3]。到目前为止，已经确定了几种机械传感器，如连接蛋白，整合素，G蛋白偶联受体（GPCR），离子载体，G蛋白，机械敏感酶和初级纤毛。最近的一项研究表明，血流诱导的EC极化缺陷可能与心血管疾病如动脉粥样硬化有关[4]。众所周知，EC是极化的，在直动脉段中平行于流动方向伸长，这被认为是降低流动阻力并触发EC中的促生存信号。相反，在具有扰动流和低剪切应力的区域中，EC具有较少的极化形式，并且不平行于血管轴定位。这种拓扑结构导致EC暴露于更高的剪切应力梯度，并使EC更容易发生动脉粥样硬化[4]。由于胚胎的小形状和相对透明性，斑马鱼为发育生物学和基于成像的研究提供了强大的系统[5]。在血管内皮细胞中表达EGFP的转基因斑马鱼用于视觉检查心脏和血管发育等过程。最近，Kwon
Cellular polarization is common to many types of cells, such as vascular endothelial cells (ECs), macrophages, and epithelial cells [1]. An individual cell has opposite sides and the directions of imaginary axes connecting opposite sides are highly coordinated. This coordination of the polarization axes is essential for the function of organs, named planar cell polarity (PCP)[2]. It occurs when cell organelles, cytoskeleton, and/or adhesion complexes display unidirectional organization along an axis. The ECs are continuously exposed to shear stress, and they directly exhibit profound morphological adaptations, such as planar cell polarization, elongation, and alignment of microtubules. In addition, the state of cell junctions and dynamic rearrangements of cytoskeleton are important for the establishment of flow-induced EC polarization, which is a significant determinant of maintaining vascular homeostasis. The alignment of ECs in the orientation of flow requires the sensibility of mechanical shear stress and the conversion of these stimuli to biochemical signals, which mediate functional changes and cytoskeletal remodeling [3]. Till now, several mechanosensors have been identified, such as junctional proteins, integrins, G-protein-coupled receptors (GPCRs), ion carriers, G-proteins, mechanosensitive enzymes, and primary cilia. A recent study indicates that defects in flow-induced EC polarization may be associated with cardiovascular diseases such as atherosclerosis [4]. It is well known that ECs are polarized, elongating parallel to the flow orientation in the straight arterial segments, which is deemed to reduce flow resistance and trigger prosurvival signals in ECs. Conversely, in the areas with disturbed flow and low shear stress, ECs have less polarized form and are not located parallel to the vascular axis. Such topology results in exposure of ECs to higher shear stress gradients and makes ECs more susceptible to atherosclerosis [4].Due to the small shape and relative transparency of embryos, zebrafish provides a powerful system for developmental biology and imaging-based studies [5]. Transgenic zebrafish that express EGFP in vascular endothelial cells was used for the visual examination of processes such as heart and vascular development. Recently, Kwon