Upregulation of thrombomodulin expression by activation of farnesoid X receptor in vascular endothelial cells
Upregulation of thrombomodulin expression by activation of farnesoid X receptor in vascular endothelial cells
复制标题
通过激活血管内皮细胞中的法尼醇 X 受体来上调血栓调节蛋白的表达。
DOI：
10.1016/j.ejphar.2013.08.020
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发表时间：
2013-10-15
影响因子：
5
通讯作者：
He, Fengtian
中科院分区：
文献类型：
--
作者：
He, Xie;Xu, Zhizhen;He, Fengtian
血栓调节蛋白（TM）作为血管内皮细胞（VEC）表面的血管保护分子，通过抑制细胞增殖、粘附和炎症反应来维持内皮微环境。法尼醇X受体（FXR）是一种核受体（NR），最初被认为是胆汁酸激活的转录因子，不仅调节代谢稳态，而且影响胆固醇转运、血管张力和炎症反应。最近的研究表明，TM的表达上调了几个NR。然而，目前尚不清楚FXR和TM之间是否存在联系。我们的研究表明，TM的表达和活性上调FXR激活血管内皮细胞。报告基因分析表明，FXR的激活显着增强人TM基因启动子的转录活性。电泳迁移率改变和染色质免疫沉淀分析表明，FXR通过与TM基因启动子区的一个新的FXR反应元件（FXRE）--一个反向重复DNA基序IR 8（-503 AGGTCCLcccaaagTGCCCT-484）结合来诱导TM的表达。这些结果表明，FXR可能作为一种新的调控TM在血管内皮细胞中表达和活性的分子Larger，这可能有助于设计针对FXR/TM通路的相关疾病的治疗策略。(C)2013 Elsevier B. V.保留所有紧身衣
Thrombomodulin (TM) serves as a vasoprotective molecule on the surface of vascular endothelial cells (VECs) to maintain the endothelial microenvironment by suppressing cellular proliferation, adhesion and inflammatory responses. Famesoid X receptor (FXR), a nuclear receptor (NR) and originally considered as a bile acid activated transcriptional factor, not only regulates metabolism homeostasis, but also influences cholesterol transport, vascular tension, and inflammation. Recent studies have shown that TM expression is upregulated by several NRs. However, it is unknown whether there is a link between FXR and TM. Our sLudies demonstrated that TM expression and activity were up-regulated by FXR activation in VECs. Reporter assays showed that FXR activation significantly enhanced the transcriptional activity of human TM gene promoter. Elecrophorclic mobility shift and chromatin irnmunoprecipilarion assays indicated that FXR induced TM expression by binding to a novel FXR-responsive element (FXRE), an inverted repeal DNA motif, IR8 (-503 AGGTCCLcccaaagTGCCCT-484) in the promoter region of TM gene. These results suggest that FXR may serve as a novel molecular Larger for manipulating TM expression and activity in VECs, which may be helpful for designing the therapeutic strategies to the treatment of associated diseases by targeting FXR/TM pathway. (C) 2013 Elsevier B.V. All tights reserved