...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Circulation research: a journal of the American Heart Association >A receptor-specific function for Notch2 in mediating vascular smooth muscle cell growth arrest through cyclin-dependent kinase inhibitor 1B
【24h】

A receptor-specific function for Notch2 in mediating vascular smooth muscle cell growth arrest through cyclin-dependent kinase inhibitor 1B

机译：Notch2受体特异性功能通过细胞周期蛋白依赖性激酶抑制剂1B介导血管平滑肌细胞生长停滞

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

RATIONALE: Deregulated vascular smooth muscle cell (VSMC) proliferation contributes to multiple vascular pathologies, and Notch signaling regulates VSMC phenotype. OBJECTIVE: Previous work focused on Notch1 and Notch3 in VSMC during vascular disease; however, the role of Notch2 is unknown. Because injured murine carotid arteries display increased Notch2 in VSMC as compared with uninjured arteries, we sought to understand the impact of Notch2 signaling in VSMCs. METHODS AND RESULTS: In human primary VSMCs, Jagged-1 (Jag-1) significantly reduced proliferation through specific activation of Notch2. Increased levels of p27 were observed downstream of Jag-1/Notch2 signaling and were required for cell cycle exit. Jag-1 activation of Notch resulted in increased phosphorylation on serine 10, decreased ubiquitination, and prolonged half-life of p27. Jag-1/Notch2 signaling robustly decreased S-phase kinase-associated protein, an F-box protein that degrades p27 during G1. Overexpression of S-phase kinase-associated protein before Notch activation by Jag-1 suppressed the induction of p27. Additionally, increased Notch2 and p27 expression was colocalized to the nonproliferative zone of injured arteries as indicated by co-staining with proliferating cell nuclear antigen, whereas Notch3 was expressed throughout normal and injured arteries, suggesting Notch2 may negatively regulate lesion formation. CONCLUSIONS: We propose a receptor-specific function for Notch2 in regulating Jag-1-induced p27 expression and growth arrest in VSMCs. During vascular remodeling, colocalization of Notch2 and p27 to the nonproliferating region supports a model where Notch2 activation may negatively regulate VSMC proliferation to lessen the severity of the lesion. Thus, Notch2 is a potential target for control of VSMC hyperplasia.
机译：理由：血管平滑肌细胞（VSMC）增殖失调会导致多种血管病变，而Notch信号调节VSMC表型。目的：先前的研究集中于血管疾病期间VSMC中的Notch1和Notch3;但是，Notch2的作用尚不清楚。由于受伤的鼠颈动脉在VSMC中显示出Notch2升高，而未受伤的动脉相比，因此我们试图了解Notch2信号在VSMC中的影响。方法和结果：在人类原发性VSMC中，Jagged-1（Jag-1）通过Notch2的特异性激活显着降低了增殖。在Jag-1 / Notch2信号下游观察到p27水平升高，这是细胞周期退出所必需的。 Jach-1激活Notch导致丝氨酸10磷酸化增加，泛素化减少以及p27的半衰期延长。 Jag-1 / Notch2信号强烈降低S期激酶相关蛋白，一种F-box蛋白，在G1期间降解p27。 Jag-1激活Notch之前S期激酶相关蛋白的过表达抑制了p27的诱导。另外，增加的Notch2和p27表达共定位于受损动脉的非增生区，这与增生的细胞核抗原共同染色表明，而Notch3在整个正常和受损动脉中均表达，表明Notch2可能负调控病变的形成。结论：我们提出Notch2的受体特异性功能调节VSMC中Jag-1诱导的p27表达和生长停滞。在血管重塑过程中，Notch2和p27共同定位于非增殖区域可支持一个模型，其中Notch2激活可能会对VSMC增殖产生负面调节，从而减轻病变的严重程度。因此，Notch2是控制VSMC增生的潜在靶标。

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