p120 inhibits LPS/TNFα-induced endothelial Ang2 synthesis and release in an NF-κB independent fashion
p120 inhibits LPS/TNFα-induced endothelial Ang2 synthesis and release in an NF-κB independent fashion
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p120 以独立于 NF-kappa B 的方式抑制 LPS/TNF α 诱导的内皮 Ang2 合成和释放
DOI：
10.1016/j.cyto.2019.154786
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发表时间：
2019-11-01
期刊：
影响因子：
3.8
通讯作者：
Tang, Yaoqing
中科院分区：
文献类型：
--
作者：
Li, Ranran;Liu, Yiyun;Tang, Yaoqing
粘附连接蛋白p120被认为是维持血管完整性的关键，这在许多病理和疾病中是重要的，包括动脉粥样硬化、血管畸形、出血性中风、败血症等。然而，对此负责的机制并不完全清楚。在这项研究中，使用无偏见的蛋白质组学方法，其次是其他实验技术，我们确定，在HUVECs p120过表达抑制LPS/TNF α诱导的血管生成素-2（Ang 2）的表达，内皮不稳定的关键开关。有趣的是，在我们的实验系统中，p120过表达并不抑制LPS/TNF α诱导的粘附分子/细胞因子包括VCAM-1、ICAM-1、E-选择素、MCP-1、IL-8和IL-6的表达。此外，这种p120介导的Ang 2抑制是以NF-κ B非依赖性方式，可能通过转录因子Ets 1。我们的研究结果表明，p120通过分泌信号影响血管完整性，为p120介导的血管稳定性机制提供了新的见解。
Adherens junction protein p120 is thought to be crucial for maintaining vascular integrity, which is important in many pathologies and diseases including atherosclerosis, vascular malformations, hemorrhagic stroke, sepsis and others. However, the mechanisms responsible for this is not completely understood. In this study, using an unbiased proteomics approach, followed by other experimental techniques, we identified that in HUVECs p120 overexpression inhibits LPS/TNF alpha-induced angiopoietin-2 (Ang2) expression, a key switch of endothelial destabilization. Interestingly, p120 overexpression did not inhibit LPS/TNF alpha-induced expression of adhesion molecules/cytokines including VCAM-1, ICAM-1, E-selectin, MCP-1, IL-8 and IL-6 in our experimental system. Furthermore, this p120-mediated repression of Ang2 is in an NF-kappa B independent manner, possibly via transcription factor Ets1. Our results demonstrate that p120 influences vascular integrity by secreted signals, providing new insights into the mechanisms of p120-mediated vascular stability.