骨桥蛋白参与血管紧张素Ⅱ诱导的血管平滑肌细胞迁移  

Ang Ⅱ-induced Migration of Vascular Smooth Muscle Cells Involves Osteopontin

作　　者：傅国香[1] 朱鼎良[1] 刘建军[1] 高平进[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院上海市高血压研究所,上海200025

出　　处：《高血压杂志》2006年第4期277-280,共4页Chinese Journal of Hypertension

基　　金：国家重点基础研究发展规划项目(G2000056904);国家自然科学基金项目(30270544)

摘　　要：目的检测血管紧张素Ⅱ(AngⅡ)对骨桥蛋白(OPN)表达的影响及其涉及的信号传导途径,并探讨OPN在AngⅡ诱导中膜平滑肌细胞(VSMCs)迁移中的作用。方法采用贴壁法培养SD大鼠胸主动脉的VSMCs。以免疫印迹(Western blot)法检测OPN表达。运用Transwell观察反义OPN在AngⅡ诱导的VSMCs迁移中的作用。结果(1)体外培养的大鼠VSMCs在基础状态下表达一定水平的OPN蛋白,经10-7mol/L AngⅡ诱导24 h后,OPN蛋白水平与对照组相比增加1.3倍(P<0.05);(2)预先给予AngⅡ1型(AT1)受体拮抗剂氯沙坦(losartan)、胞外信号调节激酶(ERK)抑制剂PD98059和P38丝裂原活化蛋白激酶(MAPK)抑制剂SB202190后,AngⅡ诱导的OPN的表达分别下降44.2%、23.6%及72.5%(P<0.05),而其2型(AT2)受体拮抗剂PD123319对OPN的表达没有影响。(3)反义OPN可以明显抑制AngⅡ诱导的VSMCs迁移(每个视野平均迁移细胞数目26.34±5.47 vs 50.23±6.12,P<0.05),而OPN正义、错配义组无此变化。结论(1)AngⅡ上调VSMCs中OPN的表达;(2)AT1受体、ERK和P38MAPK信号系统参与AngⅡ诱导的OPN表达。(3)OPN参与AngⅡ诱导的VSMCs迁移。Objective To investigate the effect of angiotensin Ⅱ （AngⅡ）on OPN expression and the role of OPN in vascular smooth muscle cells （VSMCs） migration induced by Ang Ⅱ. Methods The VSMCs were isolated from rat thoracic aorta. OPN expression was detected by Western blots. OPN antisense oligonueleotides were employed to investigate the role of OPN in cell migration by the method of Transwell. Results （1） Low level of OPN protein was expressed in cultured VSMCs. The Ang Ⅱ treated-VSMC for 24 h significantly increased OPN expression by 1.3-fold compared with the controls （P〈0.05） ; （2） AT1 receptor antagonist, losartan, ERK inhibitor PD98059 and P38 MAPK inhibitor SB202190 inhibited the effect of Ang Ⅱ by 44.2%, 23.6% and 72.5% respectively, whereas on effect was found by AT2 receptor antagonist PD123319; （3） OPN antisense oligonueleotides inhibited VSMCs migration compared with Ang Ⅱ group （26.34±5. 47 vs 50.23±6.12 cells/field, P〈0.05）, in controst without no changes by sense and mismatch OPN oligonueleotides. Conclusion （1）Ang Ⅱ up-regulate OPN expression in VSMCs; （2） AT1 receptor, ERK and P38 mitogen-activated protein kinase pathway （MAPK） signaling were involved in the OPN expression induced by Ang Ⅱ ; （3） OPN was involved in VSMCs migration induced by Ang Ⅱ.

关 键 词：平滑肌细胞 骨桥蛋白 血管紧张素Ⅱ 细胞迁移 

分 类 号：R544.1[医药卫生—心血管疾病]