Upregulation of Neogenin-1 by a CREB1-BAF47 Complex in Vascular Endothelial Cells is Implicated in Atherogenesis.
Upregulation of Neogenin-1 by a CREB1-BAF47 Complex in Vascular Endothelial Cells is Implicated in Atherogenesis.
复制标题
血管内皮细胞中 CREB1-BAF47 复合物对 Neogenin-1 的上调与动脉粥样硬化有关
DOI：
10.3389/fcell.2022.803029
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发表时间：
2022
影响因子：
5.5
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Li N;Liu H;Xue Y;Chen J;Kong X;Zhang Y
动脉粥样硬化通常被认为是一种人类慢性炎症病理，其中内皮功能障碍起着重要作用。在这里，我们研究了neogenin 1 （Neo-1）在氧化低密度脂蛋白（oxLDL）诱导的内皮功能障碍中的作用，重点是其转录调控。我们报道了oxLDL在永生化血管内皮细胞和原代主动脉内皮细胞中上调Neo-1的表达。Neo-1敲除减弱，而Neo-1过表达增强了oxldl诱导的白细胞对内皮细胞的粘附。Neo-1通过调节核因子κB （NF-κB）活性来改变粘附分子的表达，从而调节内皮细胞与白细胞的相互作用。用阻断抗体阻断Neo-1可改善Apoe−/−小鼠的动脉粥样硬化。独创性途径分析结合验证试验证实，cAMP反应元件结合蛋白1 （CREB1）和brg1相关因子47 （BAF47）介导oxLDL诱导的Neo-1上调。CREB1与BAF47相互作用，将BAF47招募到Neo-1近端启动子，导致Neo-1反式激活。总之，我们的数据描述了血管内皮细胞中Neo-1激活的一种新的转录机制，这种机制可能导致内皮功能障碍和动脉粥样硬化。
Atherosclerosis is generally considered a human pathology of chronic inflammation, to which endothelial dysfunction plays an important role. Here we investigated the role of neogenin 1 (Neo-1) in oxidized low-density lipoprotein (oxLDL) induced endothelial dysfunction focusing on its transcriptional regulation. We report that Neo-1 expression was upregulated by oxLDL in both immortalized vascular endothelial cells and primary aortic endothelial cells. Neo-1 knockdown attenuated whereas Neo-1 over-expression enhanced oxLDL-induced leukocyte adhesion to endothelial cells. Neo-1 regulated endothelial-leukocyte interaction by modulating nuclear factor kappa B (NF-κB) activity to alter the expression of adhesion molecules. Neo-1 blockade with a blocking antibody ameliorated atherogenesis in Apoe −/− mice fed a Western diet. Ingenuity pathway analysis combined with validation assays confirmed that cAMP response element binding protein 1 (CREB1) and Brg1-associated factor 47 (BAF47) mediated oxLDL induced Neo-1 upregulation. CREB1 interacted with BAF47 and recruited BAF47 to the proximal Neo-1 promoter leading to Neo-1 trans-activation. In conclusion, our data delineate a novel transcriptional mechanism underlying Neo-1 activation in vascular endothelial cells that might contribute to endothelial dysfunction and atherosclerosis.
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影响因子：
20.1
作者：
Libby P;Hansson GK
通讯作者：
Hansson GK
影响因子：
5.5
作者：
Huangfu N;Wang Y;Xu Z;Zheng W;Tao C;Li Z;Hu Y;Chen X
通讯作者：
Chen X
影响因子：
20.1
作者：
Gimbrone MA Jr;García-Cardeña G
通讯作者：
García-Cardeña G
影响因子：
5.5
作者：
Liao J;An X;Yang X;Lin QY;Liu S;Xie Y;Bai J;Xia YL;Li HH
通讯作者：
Li HH
影响因子：
4.4
作者：
Hadad, Nurit;Tuval, Liron;Levy, Rachel
通讯作者：
Levy, Rachel