军事医学2017，Vol.41Issue(6)：415-418,4.DOI:10.7644/j.issn.1674-9960.2017.06.002
脑血管内皮细胞中转化生长因子β以Smad4依赖方式上调Notch4
Smad4-dependent TGF-β directly up-regulates Notch4 in cerebrovascular endothelial cells
摘要
Abstract
Objective To find out whether NOTCH receptors can serve as direct downstream targets of transforming growth factor β(TGF-β)/Smad4 signaling in endothelial cells.Methods Real-time PCR and Western blotting were performed to verify whether the expression of notch1 and notch4 was regulated by TGF-β pathway.Luciferase reporter assay was employed to investigate how the promoter of notch1 and notch4 was regulated by TGF-β.Then, ChIP assay was used confirm whether the promoter of notch1 and notch4 physically interacted with SMAD protein.Results TGF-β1 and bone morphogenetic protein 4 (BMP4) treatment increased the expression of both notch1 and notch4 at the transcriptional level.In addition, SMAD4 was physically associated with the SMAD binding sites on the notch4 promoter, which was largely enhanced under the treatment of TGF-β1 and BMP4.Importantly, TGF-β1 and BMP4 failed to transactivate notch4 in the absence of endogenous SMAD4 or the SMAD binding regions on the notch4 promoter.Conclusion The expression of NOTCH receptor can be directly up-regulated by SMAD4-mediated TGF-β/BMP signaling in cerebrovascular endothelial cells.关键词
转化生长因子β/骨形态发生蛋白质类/SMAD4/NOTCH/内皮细胞Key words
transforming growth factor-β/bone morphogenetic proteins/SMAD4/NOTCH/endothelial cells分类
医药卫生引用本文复制引用
杨桂美,李芳菲,王友亮,王俊,兰雨..脑血管内皮细胞中转化生长因子β以Smad4依赖方式上调Notch4[J].军事医学,2017,41(6):415-418,4.基金项目
国家自然科学基金资助项目(31301203,81370596,91439128) （31301203,81370596,91439128）
