中国病理生理杂志2011,Vol.27Issue(3):443-449,7.DOI:10.3969/j.issn.1000-4718.2011.03.005
大鼠肺动脉平滑肌细胞Rho激酶对p-Smad1核迁移的作用及机制
Effects of Rho kinase on p-Smad1 nuclear translocation in rat pulmonary artery smooth muscle cells
摘要
Abstract
AIM: To explore the mechanism of bone morphogenetic protein ( BMP ) and Rho kinase signal pathways on the proliferation of pulmonary artery smooth muscle cells.METHODS: Pulmonary smooth muscle cells were isolated from the rat distal pulmonary artery and cultured.BMP and Rho kinase pathways were activated by BMP -2 and platelet - derived growth factor BB( PDGF - BB ) , respectively.Rho kinase inhihitor Y - 27632 and MEK inhibitor U0126were also used.Immunofluorescent staining was applied to observe p - Smad1 distrihution across the nucleus, and the cells with positive p - Smad1 nuclear accumulation were counted and the nuclear translocation rate was calculated.The total p Smad1 and its distribution across the nucleus were quantitatively determined by Western blotting.The cell proliferation was analyzed by CCK -8 assay.RESULTS : Exposure to BMP - 2 significantly increased both the total amount of p - Smad1and its nuclear accumulation in pulmonary smooth muscle cells.Pretreatment with PDGF - BB significantly decreased the nuclear accumulation of p - Smad1 induced by BMP - 2 without decrease of total p - Smad1.However, pretreatment with Y - 27632 or U0126 reversed the inhibitory effect of PDGF - BB on p - Smad1 nuclear accumulation.BMP - 2 significantly inhibited the cell proliferation, but PDGF - BB hlocked the effect of BMP - 2 and significantly increased the cell proliferation.After pretreated with Y - 27632 or U0126, the PDGF - BB - activated cell proliferation was suppressed.CONCLUSION : PDGF - BB - activated Rho kinase inhibits BMP - 2 - induced p - Smad1 nuclear translocation via MEK/ERK1/2 ,and increases pulmonary artery smooth muscle cell proliferation.关键词
肺动脉/平滑肌细胞/Rho激酶/骨形态发生蛋白质2/p-Smad1核迁移分类
医药卫生引用本文复制引用
李春香,李福海,夏伟,时庆,汪大琨..大鼠肺动脉平滑肌细胞Rho激酶对p-Smad1核迁移的作用及机制[J].中国病理生理杂志,2011,27(3):443-449,7.基金项目
山东省优秀中青年科学家科研奖励基金资助项目(No.2008BS03017) (No.2008BS03017)