...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >E-selectin is required for the antiangiogenic activity of endostatin.
【24h】

E-selectin is required for the antiangiogenic activity of endostatin.

机译：E-选择素是内皮抑素的抗血管生成活性所必需的。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Endostatin, a 20-kDa fragment of collagen XVIII, is a potent angiogenesis inhibitor. E-selectin, an inducible leukocyte adhesion molecule specifically expressed by endothelial cells, has also been implicated in angiogenesis. By using in vivo, ex vivo, and in vitro angiogenic assays, we investigated the functional relationship between endostatin and E-selectin. In corneal micropocket assays, recombinant endostatin administered i.p. by osmotic pump inhibited basic fibroblast growth factor-induced angiogenesis in WT, but not E-selectin-deficient, mice. Similarly, endostatin inhibited vascular endothelial growth factor-stimulated endothelial sprout formation from aortic rings dissected from WT but not from E-selectin-deficient mice. To further explore this apparent requirement for E-selectin in endostatin action, we manipulated E-selectin expression in cultured human endothelial cells. When E-selectin was induced by IL-1beta, or lipopolysaccharide, human umbilical vein endothelial cells and human dermal microvascular endothelial cells each became markedly more sensitive to inhibition by endostatin in a vascular endothelial growth factor-induced cell migration assay. To dissociate E-selectin expression from other consequences of endothelial activation, human umbilical vein endothelial cells were transduced with an adenoviral human E-selectin expression construct; these cells also showed increased sensitivity to endostatin, and this effect required the E-selectin cytoplasmic domain. Taken together, these results indicate that E-selectin is required for the antiangiogenic activity of endostatin in vivo and ex vivo and confers endostatin sensitivity to nonresponsive human endothelial cells in vitro. E-selectin may be a useful predictor and modulator of endostatin efficacy in antiangiogenic therapy.
机译：内皮抑素是胶原蛋白XVIII的20 kDa片段，是一种有效的血管生成抑制剂。 E-选择蛋白，一种由内皮细胞特异性表达的诱导型白细胞粘附分子，也与血管生成有关。通过使用体内，离体和体外血管生成测定，我们调查了内皮抑素和E选择素之间的功能关系。在角膜微囊测定中，重组内皮抑素经腹膜内给药。通过渗透泵抑制WT中的碱性成纤维细胞生长因子诱导的血管生成，但不抑制E-选择蛋白缺陷的小鼠。类似地，内皮抑素抑制了从WT切开的主动脉环上的血管内皮生长因子刺激的内皮发芽的形成，但没有从E-选择素缺陷型小鼠切下。为了进一步探讨内皮抑素作用中E-选择素的这一明显要求，我们操纵了E-选择素在培养的人内皮细胞中的表达。当IL-1β或脂多糖诱导E-选择素时，在血管内皮生长因子诱导的细胞迁移测定中，人脐静脉内皮细胞和人皮肤微血管内皮细胞对内皮抑素的抑制作用变得更加敏感。为了使E-选择蛋白表达与内皮激活的其他结果分离，用人E-选择蛋白表达腺病毒构建体转导人脐静脉内皮细胞。这些细胞还显示出对内皮抑素的敏感性增加，这种作用需要E-选择素胞质域。两者合计，这些结果表明E-选择素是内皮抑素在体内和体外的抗血管生成活性所必需的，并且赋予内皮抑素对体外无反应的人内皮细胞敏感。 E-选择蛋白可能是内皮抑素在抗血管生成治疗中有用的预测剂和调节剂。

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