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血管内核因子-κB-依赖的调节动脉发生和分支
Daniela Tirziu1, Irina M Jaba, Pengchun Yu
1Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT 06520-8017, USA.
Circulation
|October 24, 2012
概括
核因子-卡帕B (NFκB) 调节血管发育. 抑制NFκB会导致过度分支和不成熟的血管,影响组织输液和网络复杂性.
科学领域:
- 心血管生物学 心血管生物学
- 分子生物学分子生物学
- 发育生物学 发展生物学
背景情况:
- 动脉生成和附带形成是复杂的过程,涉及协调的血管发育.
- 控制这些血管过程的关键调节因素在很大程度上仍未确定.
研究的目的:
- 研究核因子-卡帕B (NFκB) 在调节动脉生成和附带形成中的作用.
- 阐明NFκB影响血管网络发育和成熟的分子机制.
主要方法:
- 使用了NFκB激活的抑制剂 (IκBαSR) 与内皮特异性的可诱导促进剂.
- 在发育,成人和体外环境中选择性抑制内皮细胞NFκB激活.
- 分析了分子变化,包括粘附分子表达,单细胞流入,HIF-1α和DLL4/Notch信号.
主要成果:
- 抑制NFκB导致过度分支的动脉网络与不成熟的血管和糟糕的输液.
- 抑制NFκB降低了粘附分子,单细胞流入,缺氧诱导因子-1α (HIF-1α) 和δ类联结物4 (DLL4) 的表达.
- 减少DLL4表达 损害了Notch信号,导致血管分支增加; Jagged-1治疗使网络大小正常化.
结论:
- NFκB被确定为发育和成人动脉生成和附带形成的关键调节者.
- 通过调节依赖HIF-1α的VEGF-A和PDGF-BB的表达,NFκB控制了血管网络的发展和成熟.
- 此外,NFκB还调节DLL4的表达,从而确定动脉附带网络的规模和复杂性.
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