...
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Rho activity critically and selectively regulates endothelial cell organization during angiogenesis
【24h】

Rho activity critically and selectively regulates endothelial cell organization during angiogenesis

机译:Rho活性关键和选择性地调节血管生成过程中的内皮细胞组织。

获取原文
获取原文并翻译 | 示例
           

摘要

The mechanisms that control organization of endothelial cells (ECs) into new blood vessels are poorly understood. We hypothesized that the GTPase Rho, which regulates cytoskeletal architecture, is important for EC organization during neovascularization. To test this hypothesis, we designed a highly versatile mouse skin model that used vascular endothelial growth factor-expressing cells together with packaging cells producing retroviruses encoding RhoA GTPase mutants. In this animal model, dominant negative N19RhoA selectively impaired assembly of ECs into new blood vessels; and, in contrast, active V14RhoA stimulated ECs to form blood vessels with functional lumens. In vitro, dominant negative N19RhoA reduced EC actin stress fibers and prevented ECs from contracting and reorganizing into precapillary cords within collagen gels. In contrast, active V14RhoA promoted EC stress fiber formation, contractility, and organization into cords. Neither N19RhoA nor V14RhoA significantly affected EC proliferation or migration in vitro; and, similarly, neither mutant significantly affected EC density during angiogenesis in vivo. Thus, these studies identify a critical and selective role for Rho activity in regulating EC assembly into new blood vessels, and they identify both negative and positive manipulation of Rho activity, respectively, as strategies for suppressing or promoting the organizational stages of neovascularization.
机译:人们很少了解控制内皮细胞(EC)进入新血管的组织机制。我们假设,调节细胞骨架结构的GTPase Rho对于新血管形成过程中的EC组织很重要。为了检验该假设,我们设计了一种高度通用的小鼠皮肤模型,该模型使用表达血管内皮生长因子的细胞以及产生编码RhoA GTPase突变体的逆转录病毒的包装细胞。在这种动物模型中,显性阴性N19RhoA选择性地损害了EC组装入新血管的能力。与此相反,活性V14RhoA刺激EC形成具有功能腔的血管。在体外,显性阴性N19RhoA减少EC肌动蛋白应力纤维并阻止EC收缩并重组为胶原蛋白凝胶内的毛细血管前索。相反,活性V14RhoA促进EC应力纤维的形成,收缩性和组织成帘线。 N19RhoA和V14RhoA均未在体外显着影响EC增殖或迁移。同样,在体内血管生成过程中,这两个突变体均未显着影响EC密度。因此,这些研究确定了Rho活性在调节EC组装入新血管中的关键和选择性作用,并且分别确定了Rho活性的负向和正向操纵,作为抑制或促进新血管形成的组织阶段的策略。

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