摘要
目的探讨转化生长因子β1/Smad(TGF-β1/Smad)信号通路参与氧化型低密度脂蛋白(ox-LDL)刺激的人脐静脉内皮细胞血管细胞黏附分子1(VCAM-1)和细胞间黏附分子1(ICAM-1)表达的分子机制。方法体外培养人脐静脉内皮细胞,加入ox-LDL(0.1 g/L)刺激细胞,用Western blot检测TGF-β1、Smad3磷酸化、VCAM-1和ICAM-1的表达。结果 ox-LDL明显增加人脐静脉内皮细胞VCAM-1和ICAM-1的表达(P<0.05)。ox-LDL激活人脐静脉内皮细胞TGF-β1/Smad信号通路,TGF-β1表达明显增加,Smad3磷酸化明显增强。细胞核提取物分析表明,磷酸化的Smad3在细胞核表达增加。特异性Smad3磷酸化抑制剂SIS3以浓度依赖方式抑制ox-LDL刺激的Smad3磷酸化(P<0.05),且VCAM-1和ICAM-1的表达增加(P<0.05)。结论 TGF-β1/Smad信号通路参与调节氧化型低密度脂蛋白刺激的内皮细胞炎症蛋白表达,抑制Smad3磷酸化反而增加炎症蛋白表达,提示TGF-β1/Smad3通道活化具有抑制ox-LDL刺激的内皮细胞炎症蛋白表达的影响。
Aim To investigate the molecular mechanism of inflammatory protein expression via transforming growth factor-β1（TGF-β1）/Smad pathway in ox-LDL-stimulated human umbilical vein endothelial cells（HUVEC）.Methods HUVEC were treated with 0.1 g/L of ox-LDL.TGF-β1,Smad3,VCAM-1 and ICAM-1 protein expression,and Smad3 phosphorylation were detemined by Western blot.Results ox-LDL obviously increased the expression of VCAM-1 and ICAM-1 in HUVEC.TGF-β1 expression and Smad3 phosphorylation were enhanced in ox-LDL-stimulated HUVEC.Nuclear extract analysis showed that the phosphorylated Smad3 expression was increased in ox-LDL-treated cells.SIS3（a specific inhibitor of Smad3） inhibited Smad3 phosphorylation in a dose-dependent manner,however,VCAM-1 and ICAM-1 expression were increased in ox-LDL-treated cells.Conclusions TGF-β1/Smad signaling involved in the regulation of inflammatory protein expression in HUVEC induced by ox-LDL,the inhibition of Smad3 phosphorylation increased the expression of inflammatory protein,suggesting that TGF-β1/Smad3 signaling repressed the inflammatory protein expression in ox-LDL-treated endothelial cells.
出处
《中国动脉硬化杂志》
CAS
CSCD
北大核心
2012年第3期203-206,共4页
Chinese Journal of Arteriosclerosis
基金
国家自然科学基金项目(青年基金30900627)
关键词
转化生长因子β1
SMAD3
人脐静脉内皮细胞
血管细胞黏附分子1
细胞间黏附分子1
Transforming Growth Factor-β1
Smad3
Human Umbilical Vein Endothelial Cells
Vascular Cell Adhesion Molecular-1
Intercellular Cell Adhesion Molecule-1
