ERK信号通路调控二氧化硅诱导的人支气管上皮细胞上皮-间质转化  被引量:1

ERK signaling pathway mediated epithelial-mesenchymal transition induced by SiO_2 in human bronchial epithelial cells

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作  者:高振芹[1] 胡永斌[1] 彭劲武[1] 邓征浩[1] 梁冠男[1] 蒋海鹰[1] 周建华[1] 

机构地区:[1]中南大学基础医学院病理学系,长沙410013

出  处:《中南大学学报(医学版)》2011年第11期1085-1089,共5页Journal of Central South University :Medical Science

基  金:国家自然科学基金(30700661);湖南省自然科学基金(06JJ2098;10JJ5036)~~

摘  要:目的:探讨细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)信号通路在二氧化硅(SiO2)诱导人支气管上皮细胞(human bronchial epithelial cells,HBEC)上皮-间质转型(epithelial-mesenchymaltransition,EMT)中的作用机制。方法:SiO2(0~300μg/mL)处理HBEC 72 h,或不同浓度的U0126(0~30μmol/L)干预1 h后再行200μg/mL SiO2刺激72 h,Western印迹检测E-cadherin和α-平滑肌肌动蛋白(α-SMA)表达的改变;使用丝裂原活化蛋白激酶(MAPK)活性检测试剂盒检测SiO2(200μg/mL)处理HBEC(0~8 h)后ERK激活情况。结果:SiO2刺激HBEC后,E-cadherin蛋白表达水平逐渐下调,以300μg/mL时最为明显(P<0.01),α-SMA蛋白表达水平逐渐上调,以200μg/mL时最为明显(P<0.01)。SiO2刺激HBEC后,ERK明显活化,ERK磷酸化水平于30 min开始升高,1 h后逐渐降低。ERK抑制剂U0126明显抑制SiO2诱导的E-cadherin和α-SMA蛋白表达的变化,浓度为30μmol/L时最为明显(P<0.01)。结论:ERK信号通路参与调控SiO2诱导的HBEC的EMT。Objective To determine the role of extracellular signal regulated kinase(ERK) signaling pathway in SiO2 induced epithelial-mesenchymal transition(EMT) in human bronchial epithelial cells(HBEC) in vitro.Methods HBEC were treated with SiO2(0-300 μg/mL) for 72 h or pretreated with U0126(0-30 μmol/L) for 1 h and then treated with 200 μg/mL SiO2 for 72 h.Western blot was used to detect the protein expression of E-cadherin and α-smooth muscle actin(α-SMA).The activity of ERK was examined by mitogen-activated protein kinase(MAPK) activity assay kit in HBEC exposing to SiO2(200 μg/mL) for 0-8 h.Results The expression of E-cadherin decreased gradually in SiO2-stimulated HBEC,and the effect was most significant at 300 μg/mL(P0.01).The expression of α-SMA increased and the effect was most evident at 200 μg/mL(P0.01).With SiO2 treatment,the activity of ERK was upregulated significantly.The phosphorylation of ERK increased at 30 min and decreased after 1 h.U0126 significantly inhibited SiO2-induced expression changes in E-cadherin and α-SMA.At 30 μmol/L,the effect was most evident(P0.01).Conclusion ERK signaling pathway mediated EMT induced by SiO2 in HBEC.

关 键 词:二氧化硅 细胞外信号调节激酶 人支气管上皮细胞 上皮-间质转型 

分 类 号:R563.9[医药卫生—呼吸系统]

 

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