Division of Cardiothoracic Surgery, University of California, San Diego, CA, 92103-8892, USA.
Adv Exp Med Biol. 2010;661:279-98. doi: 10.1007/978-1-60761-500-2_18.
Proteins of the Notch receptor family are cell surface receptors that transduce signals between neighboring cells. The Notch signaling pathway is highly evolutionarily conserved and critical for cell fate determination during embryogenesis and early postnatal life, including many aspects of vascular development. The interaction of Notch receptor with its membrane-bound ligands leads to cleavage of the receptor into an intracellular domain that translocates to the nucleus and activates the transcription factor, C-promoter binding factor 1 (CBF1; also known as Recombination signal-binding protein for immunoglobulin kappa J region, RBPJ). To date, four Notch receptors have been characterized in humans. Of these, Notch3 is expressed only in arterial smooth muscle cells in the human. The functional importance of Notch3 signaling in human vascular smooth muscle cells has been recognized. Notch3 receptor signaling has been shown in several model systems to control vascular smooth muscle cell proliferation and maintain smooth muscle cells in an undifferentiated state. This review focuses on recent findings of the role of Notch3 in regulating vascular smooth muscle cell behavior and phenotype and discusses the potential role of Notch3 signaling in the genesis of pulmonary arterial hypertension.
Notch 受体家族的蛋白是细胞表面受体，可在相邻细胞之间传递信号。Notch 信号通路高度进化保守，对于胚胎发生和出生后早期的细胞命运决定至关重要，包括血管发育的许多方面。Notch 受体与其膜结合配体的相互作用导致受体切割成一个胞内结构域，该结构域易位到细胞核并激活转录因子 C 启动子结合因子 1（CBF1；也称为免疫球蛋白 k 轻链 J 区重组信号结合蛋白，RBPJ）。迄今为止，已在人类中鉴定出四个 Notch 受体。其中，Notch3 仅在人类动脉平滑肌细胞中表达。Notch3 信号在人血管平滑肌细胞中的功能重要性已得到认可。在几个模型系统中已经表明 Notch3 受体信号可控制血管平滑肌细胞增殖并使平滑肌细胞保持未分化状态。本综述重点介绍 Notch3 在调节血管平滑肌细胞行为和表型中的作用的最新发现，并讨论 Notch3 信号在肺动脉高压发生中的潜在作用。
