Department of Cardiology, The Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, Zhejiang, China.
Mol Cell Biochem. 2013 Sep;381(1-2):283-90. doi: 10.1007/s11010-013-1713-8. Epub 2013 Jun 8.
Thymosin beta4 (Tβ4) has multi-functional roles in angiogenesis and arteriogenesis, but little is known about its mechanism. The Notch signaling pathway is important in regulation of angiogenic behavior of endothelial cells, in addition to vascular endothelial growth factor (VEGF). Whether, Tβ4 regulates angiogenesis through Notch signaling pathway is not clear. In this article, we evaluated the effect of Notch signaling in Tβ4-induced angiogenesis in human umbilical vein endothelial cell (HUVEC). Our results revealed that Tβ4 increased Notch1 and Notch4 expression in a dose and time-dependent manner. The inhibition of Notch1 or Notch4 with siRNA or the Notch receptor inhibitor DAPT significantly prevented Tβ4-induced HUVEC tube formation and lymphocyte transendothelial migration. The inhibition of Notch1 or Notch4 also blocked Tβ4-induced VEGF and HIF-1α expression. VE-cadherin is the major endothelial adhesion molecule in the control of angiogenesis. Tβ4 significantly reduced VE-cadherin expression levels in HUVEC, while the inhibition of Notch signaling prevented Tβ4-induced VE-cadherin down-regulation. The results of this study suggest that Tβ4 induces HUVEC angiogenesis through Notch signaling pathway.
胸腺素β4（Tβ4）在血管生成和动脉生成中具有多种功能作用，但对其机制知之甚少。除血管内皮生长因子（VEGF）外，Notch 信号通路在调节内皮细胞的血管生成行为中也很重要。Tβ4 是否通过 Notch 信号通路调节血管生成尚不清楚。在本文中，我们评估了 Notch 信号通路在 Tβ4 诱导的人脐静脉内皮细胞（HUVEC）血管生成中的作用。我们的结果表明，Tβ4 以剂量和时间依赖性的方式增加 Notch1 和 Notch4 的表达。用 siRNA 或 Notch 受体抑制剂 DAPT 抑制 Notch1 或 Notch4，可显著阻止 Tβ4 诱导的 HUVEC 管形成和淋巴细胞跨内皮迁移。抑制 Notch1 或 Notch4 也可阻断 Tβ4 诱导的 VEGF 和 HIF-1α 的表达。VE-钙黏蛋白是控制血管生成的主要内皮黏附分子。Tβ4 可显著降低 HUVEC 中的 VE-钙黏蛋白表达水平，而 Notch 信号通路的抑制可阻止 Tβ4 诱导的 VE-钙黏蛋白下调。本研究结果表明，Tβ4 通过 Notch 信号通路诱导 HUVEC 血管生成。
