G-protein coupled receptor 30 (GPR30): a novel regulator of endothelial inflammation.
G-protein coupled receptor 30 (GPR30): a novel regulator of endothelial inflammation.
复制标题
DOI：
10.1371/journal.pone.0052357
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Davidge ST
中科院分区：
文献类型：
--
作者：
Chakrabarti S;Davidge ST
众所周知，雌激素是一种女性荷尔蒙，具有抗炎和抗动脉粥样硬化的作用。传统上，雌激素效应被认为主要是通过经典的雌激素受体(ER)来实现的。然而，越来越多的证据表明，G蛋白偶联受体30(GPR30)是一种新的雌激素受体，可以在血管系统中介导许多雌激素效应。尽管如此，GPR30在人血管内皮细胞中的定位和功能意义仍然知之甚少。在这一背景下，我们以人脐静脉内皮细胞为模型系统，研究了GPR30的亚细胞定位和潜在的抗炎作用。炎症变化是由肿瘤坏死因子(TNF)治疗引起的，肿瘤坏死因子是一种参与动脉粥样硬化形成和许多其他炎症条件的促炎细胞因子。我们发现GPR30主要定位于内皮细胞核。选择性GPR30激动剂G-1可部分减弱肿瘤坏死因子诱导的促炎蛋白如细胞间黏附分子-1(ICAM-1)和血管细胞黏附分子-1(VCAM-1)的上调。这种作用被选择性的GPR30拮抗剂G-15完全消除，这表明它确实是以GPR30依赖的方式介导的。有趣的是，雌激素单独对肿瘤坏死因子处理的内皮细胞没有影响。经典内质网的伴随激活阻断了G-1的抗炎作用，表明GPR30与经典内质网的作用相反。我们的发现表明，内皮GPR30是一种新的炎症反应调节因子，可能成为治疗动脉粥样硬化和其他炎症性疾病的潜在靶点。
Estrogen, the female sex hormone, is known to exert anti-inflammatory and anti-atherogenic effects. Traditionally, estrogen effects were believed to be largely mediated through the classical estrogen receptors (ERs). However, there is increasing evidence that G-protein coupled receptor 30 (GPR30), a novel estrogen receptor, can mediate many estrogenic effects on the vasculature. Despite this, the localization and functional significance of GPR30 in the human vascular endothelium remains poorly understood. Given this background, we examined the subcellular location and potential anti-inflammatory roles of GPR30 using human umbilical vein endothelial cells as a model system. Inflammatory changes were induced by treatment with tumor necrosis factor (TNF), a pro-inflammatory cytokine involved in atherogenesis and many other inflammatory conditions. We found that GPR30 was located predominantly in the endothelial cell nuclei. Treatment with the selective GPR30 agonist G-1 partially attenuated the TNF induced upregulation of pro-inflammatory proteins such as intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). This effect was completely abolished by the selective GPR30 antagonist G-15, suggesting that it was indeed mediated in a GPR30 dependent manner. Interestingly, estrogen alone had no effects on TNF-treated endothelium. Concomitant activation of the classical ERs blocked the anti-inflammatory effects of G-1, indicating opposing effects of GPR30 and the classical ERs. Our findings demonstrate that endothelial GPR30 is a novel regulator of the inflammatory response which could be a potential therapeutic target against atherosclerosis and other inflammatory diseases.
登录
查看更多内容
DOI：
10.1073/pnas.90.23.11137
发表时间：
1993-12-01
影响因子：
11.1
作者：
KORPELAINEN, EI;GAMBLE, JR;LOPEZ, AF
通讯作者：
LOPEZ, AF
DOI：
10.1152/ajpregu.00595.2004
发表时间：
2005-03-01
影响因子：
2.8
作者：
Dean, SA;Tan, JH;Leenen, FHH
通讯作者：
Leenen, FHH
影响因子：
4.8
作者：
Gao, Fei;Ma, Xinghong;Das, Sanjoy K.
通讯作者：
Das, Sanjoy K.
影响因子：
1.7
作者：
Holm, Anders;Baldetorp, Bo;Nilsson, Bengt-Olof
通讯作者：
Nilsson, Bengt-Olof
影响因子：
8.3
作者：
Hinojosa-Laborde, C;Craig, T;Sandberg, K
通讯作者：
Sandberg, K