• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>EBioMedicine >Cyclic AMP Response Element Binding Protein Mediates Pathological Retinal Neovascularization via Modulating DLL4-NOTCH1 Signaling
【24h】

Cyclic AMP Response Element Binding Protein Mediates Pathological Retinal Neovascularization via Modulating DLL4-NOTCH1 Signaling

机译：环状AMP反应元件结合蛋白通过调节DLL4-NOTCH1信号介导病理性视网膜新血管形成。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Retinal neovascularization is the most common cause of moderate to severe vision loss in all age groups. Despite the use of anti-VEGFA therapies, this complication continues to cause blindness, suggesting a role for additional molecules in retinal neovascularization. Besides VEGFA and VEGFB, hypoxia induced VEGFC expression robustly. Based on this finding, we tested the role of VEGFC in pathological retinal angiogenesis. VEGFC induced proliferation, migration, sprouting and tube formation of human retinal microvascular endothelial cells (HRMVECs) and these responses require CREB-mediated DLL4 expression and NOTCH1 activation. Furthermore, down regulation of VEGFC levels substantially reduced tip cell formation and retinal neovascularization in vivo. In addition, we observed that CREB via modulating the DLL4-NOTCH1 signaling mediates VEGFC-induced tip cell formation and retinal neovascularization. In regard to upstream mechanism, we found that down regulation of p38@b levels inhibited hypoxia-induced CREB-DLL4-NOTCH1 activation, tip cell formation, sprouting and retinal neovascularization. Based on these findings, it may be suggested that VEGFC besides its role in the regulation of lymphangiogenesis also plays a role in pathological retinal angiogenesis and this effect depends on p38@b and CREB-mediated activation of DLL4-NOTCH1 signaling.
机译：视网膜新血管形成是所有年龄组中度至重度视力丧失的最常见原因。尽管使用了抗VEGFA疗法，但这种并发症继续导致失明，提示其他分子在视网膜新血管形成中的作用。除VEGFA和VEGFB外，缺氧还强烈诱导VEGFC表达。基于此发现，我们测试了VEGFC在病理性视网膜血管生成中的作用。 VEGFC诱导人视网膜微血管内皮细胞（HRMVEC）的增殖，迁移，发芽和管形成，而这些反应需要CREB介导的DLL4表达和NOTCH1激活。此外，VEGFC水平的下调实质上减少了体内的尖细胞形成和视网膜新血管形成。此外，我们观察到CREB通过调节DLL4-NOTCH1信号传导介导VEGFC诱导的尖端细胞形成和视网膜新血管形成。关于上游机制，我们发现下调p38 @ b水平抑制了低氧诱导的CREB-DLL4-NOTCH1活化，尖端细胞形成，发芽和视网膜新血管形成。基于这些发现，可能提示VEGFC除了在调节淋巴管生成中的作用外，在病理性视网膜血管生成中也起作用，并且这种作用取决于p38 @ b和CREB介导的DLL4-NOTCH1信号传导的激活。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号