TM4SF19 aggravates LPS-induced attenuation of vascular endothelial cell adherens junctions by suppressing VE-cadherin expression
TM4SF19 aggravates LPS-induced attenuation of vascular endothelial cell adherens junctions by suppressing VE-cadherin expression
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TM4SF19 通过抑制 VE-钙粘蛋白表达加剧 LPS 诱导的血管内皮细胞粘附连接减弱
DOI：
10.1016/j.bbrc.2020.08.078
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发表时间：
2020-12-17
影响因子：
3.1
通讯作者：
Wang, Qian
中科院分区：
文献类型：
--
作者：
Ding, Li;Li, Li-Min;Wang, Qian
动脉粥样硬化是一种慢性血管炎性疾病，最初始于动脉内膜病变和内皮屏障功能障碍。本研究的目的是探讨TM 4SF 19，最近发现的跨膜4L 6超家族的成员，在血管内皮细胞粘附连接的作用。我们通过免疫组化和ELISA检测发现TM 4SF 19在冠心病患者的动脉粥样硬化斑块和血清中的表达明显高于健康人。在体外，人脐静脉内皮细胞（HUVECs）被脂多糖（LPS）刺激。评估TM 4SF 19和VE-钙粘蛋白表达以及细胞粘附连接。LPS可浓度依赖性上调HUVECs中TM 4SF 19的表达，下调VE-cadherin的表达。TM 4SF 19的过表达显著加重了LPS诱导的VE-钙粘蛋白表达的减少和血管内皮细胞粘附连接的减弱。然而，当抑制TM 4SF 19的表达时，LPS诱导的VE-钙粘蛋白表达的降低和细胞粘附连接的减弱都可以显著逆转。本研究首次揭示了TM 4SF 19对内皮细胞粘附连接的影响。同时，我们的研究结果也为动脉粥样硬化性疾病提供了新的治疗策略。(C)2020爱思唯尔公司All rights reserved.
Atherosclerosis is a chronic vascular inflammatory disease that initially starts from an arterial intima lesion and endothelial barrier dysfunction. The purpose of this study was to investigate the role of TM4SF19, a recently identified member of the transmembrane 4L six superfamily, in vascular endothelial cell adherens junctions. We found TM4SF19 expression was significantly increased in atherosclerotic plaques and sera of patients with coronary heart disease (CHD) compared with healthy people by immunohistochemistry and ELISA. In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated by lipopolysaccharides (LPS). TM4SF19 and VE-cadherin expression as well as cell adherens junctions were assessed. Additionally, LPS could upregulate TM4SF19 expression and downregulate VE-cadherin expression in HUVECs in a concentration dependent manner. Overexpression of TM4SF19 substantially aggravated LPS-induced reduction of VE-cadherin expression and attenuation of vascular endothelial cell adherens junctions. However, both the decreased VE-cadherin expression and weakened cell adherens junctions induced by LPS could be dramatically reversed when the expression of TM4SF19 was depressed. This study is the first to reveal the effect of TM4SF19 on endothelial cell adherens junctions. Meanwhile, our results also provide novel therapeutic strategies for atherosclerotic diseases. (C) 2020 Elsevier Inc. All rights reserved.