Funahashi Yasuhiro, Shawber Carrie J, Vorontchikhina Marina, Sharma Anshula, Outtz Hasina H, Kitajewski Jan
Pathology, Obstetrics and Gynecology, and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA.
J Angiogenes Res. 2010 Jan 26;2(1):3. doi: 10.1186/2040-2384-2-3.
Notch is a critical regulator of angiogenesis and arterial specification. We show that ectopic expression of activated Notch1 induces endothelial morphogenesis in human umbilical vein endothelial cells (HUVEC) in a VEGFR-1-dependent manner. Notch1-mediated upregulation of VEGFR-1 in HUVEC increased their responsiveness to the VEGFR-1 specific ligand, Placental Growth Factor (PlGF). In mice and human endothelial cells, inhibition of Notch signaling resulted in decreased VEGFR-1 expression during VEGF-A-induced neovascularization. In summary, we show that Notch1 plays a role in endothelial cells by regulating VEGFR-1, a function that may be important for physiological and pathological angiogenesis.
Notch是血管生成和动脉特化的关键调节因子。我们发现，活化的Notch1的异位表达以VEGFR-1依赖的方式诱导人脐静脉内皮细胞（HUVEC）发生内皮形态发生。Notch1介导的HUVEC中VEGFR-1的上调增加了它们对VEGFR-1特异性配体胎盘生长因子（PlGF）的反应性。在小鼠和人内皮细胞中，Notch信号的抑制导致在VEGF-A诱导的新生血管形成过程中VEGFR-1表达降低。总之，我们表明Notch1通过调节VEGFR-1在内皮细胞中发挥作用，这一功能可能对生理和病理血管生成很重要。
