通过Notch1发送的Dll4信号调节了血管新生过程中尖端细胞的形成
Mats Hellström1, Li-Kun Phng, Jennifer J Hofmann
1AngioGenetics Sweden AB, Scheeles väg 2, SE-171 77 Stockholm, Sweden. mats.hellstrom@ki.se
Nature
|January 30, 2007
概括
德尔塔样4 (Dll4) -Notch1信号控制在发芽血管生成期间内皮末端细胞的数量. 这种机制确保了老鼠视网膜中适当的血管形成和分支.
科学领域:
- 发育生物学是发展生物学.
- 细胞信号传递 细胞信号传递
- 血管新生研究研究
背景情况:
- 发芽血管生成涉及内皮尖细胞指导新的血管生长,由血管内皮生长因子 (VEGF-A) 驱动.
- 确定每个芽端细胞数量的确切机制尚不清楚.
研究的目的:
- 调查三角形状4 (Dll4) -Notch1信号在调节视网膜血管生成期间尖端细胞数量的作用.
- 了解这种信号通路如何控制血管发芽和分支模式.
主要方法:
- 使用玛分泌酶抑制剂抑制诺奇信号传递.
- 在小鼠模型中进行基因操纵,包括Dll4哈普洛缺陷和内皮特异性Notch1删除.
- 用一种可溶性1来激活Notch信号.
主要成果:
- 缺口信号抑制导致尖端细胞数量的增加.
- 相反,Notch激活导致尖端细胞减少,并减少了血管分支.
- Dll4和Notch信号显示出在生长的视网膜血管中的马赛克分布,Notch1删除的细胞有利于尖端细胞命运.
结论:
- Dll4-Notch1信号传递起到关键的调节作用,限制了对VEGF的反应中尖端细胞的形成.
- 这一途径在尖端和茎细胞之间建立了正确的平衡,以实现有效的血管生成.
- 调节Dll4或Notch信号的调节剂可能是控制血管生成的潜在治疗剂.
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