Takebe Noriyoshi, Sugita Yoshito, Takada Shigeki, Muraki Kazue, Dunwoodie Sally L, Hojo Masato, Miyamoto Susumu, Arakawa Yoshiki, Tanigaki Kenji
Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Research Institute, Shiga Medical Center, Shiga, Japan.
Sci Rep. 2025 Aug 24;15(1):31153. doi: 10.1038/s41598-025-17225-5.
Notch signaling is critical for vascular development. However, the functions vary significantly depending on organs and the developmental stage. The adult vasculature is less susceptible to Notch signaling inhibition. Vessels in the adult pituitary posterior lobes maintain characteristics of immature vessels, such as sensitivity to VEGF. Here, we show that Notch4 deficiency caused reduction of vascular density, vascular branch length and the number of branching points and the larger radius vessels in the adult pituitary posterior lobes using the automated vascular image analysis method. Upregulation of NR2F2 by Notch4 loss induced arteriovenous identity deficiency. Notch4 has been reported to have dual roles on the regulation of RBP-J-mediated transcription. DAPT is a γ-secretase inhibitor, which inhibits Notch signaling. DAPT-treated adult pituitary posterior lobes showed similar vascular phenotypes to that of Notch4 knockout mice except for the length of affected larger radius vessels, suggesting the importance of RBP-J-mediated transcription in vascular maintenance of the adult pituitary posterior lobes. These data indicate that the maintenance of adult pituitary posterior lobe vasculature requires Notch signaling.
Notch信号通路对血管发育至关重要。然而，其功能因器官和发育阶段的不同而有显著差异。成体血管对Notch信号通路抑制的敏感性较低。成年垂体后叶中的血管保持着未成熟血管的特征，如对血管内皮生长因子（VEGF）敏感。在此，我们使用自动血管图像分析方法表明，Notch4缺陷导致成年垂体后叶血管密度降低、血管分支长度和分支点数减少，以及较大半径血管减少。Notch4缺失导致的NR2F2上调诱导动静脉身份缺陷。据报道，Notch4在调节RBP-J介导的转录方面具有双重作用。DAPT是一种γ-分泌酶抑制剂，可抑制Notch信号通路。除了受影响的较大半径血管的长度外，经DAPT处理的成年垂体后叶显示出与Notch4基因敲除小鼠相似的血管表型，这表明RBP-J介导的转录在成年垂体后叶血管维持中的重要性。这些数据表明，成年垂体后叶血管系统的维持需要Notch信号通路。
