p38 MAPK和JNK信号通道在TGF-β1诱导的肺泡上皮细胞上皮-间质转化中的意义  

Roles of p38 MAPK and JNK in TGF-β1-induced alveolar epithelial to mesenchymal transition

作　　者：陈海华[1] 周贤龙[1] 施余露[1] 杨炯[1] 

机构地区：[1]武汉大学中南医院呼吸内科,430071

出　　处：《国际呼吸杂志》2014年第20期1544-1550,共7页International Journal of Respiration

摘　　要：目的 探讨p38丝裂原活化蛋白激酶（p38 MAPK）和c-Jun氨基端激酶（JNK）信号通道在转化生长因子β1 （TGF-β1）诱导的人肺泡上皮细胞上皮-间质转化（epithelial to mesenchymal transition,EMT）中的意义,从而进一步揭示肺纤维化的发病机制.方法 使用TGF-β1诱导A549细胞EMT,分别在蛋白水平（使用p38 MAPK抑制剂SB203580和JNK抑制剂SP600125）和RNA水平（RNA干扰）抑制p38 MAPK和JNK信号通道,检测抑制后A549细胞的p38 MAPK和JNK的蛋白和mRNA,以及间质细胞表型蛋白包括结蛋白、波形蛋白、α-平滑肌肌动蛋白和上皮细胞表型蛋白包括E-钙黏素、紧密连接蛋白-1、水通道蛋白-5的表达.结果 TGF-β1可以诱导A549细胞EMT,表现为间质细胞表型蛋白表达的增加和上皮细胞表型蛋白表达的减少,这一过程p38 MAPK和JNK通道表达也增加,无论蛋白水平抑制或基因沉默p38 MAPK和JNK均可减轻A549细胞的EMT.结论 p38 MAPK和JNK信号通道在TGF-β1诱导的A549细胞EMT过程中起重要作用.Objective To investigate the roles of p38 MAPK and JNK in transforming growth factor-β1 （TGF-β1）-induced human alveolar epithelial to mesenchymal transition （EMT）,and to demonstrate the possible molecular mechanism of idiopathic pulmonary fibrosis.Methods A549 cells were treated with TGF-β1 （3 μg/L） for 48 hours to induce EMT.The expressions of mesenchymal phenotypic markers including desmin,α-smooth muscle actin （α-SMA） and vimentin,and expressions of epithelial phenotypic markers including E cadherin,zonula occludens-1 （ZO-1） and aquaporin-5 （AQP-5） were detected by Western blot.The role of p38 MAPK and JNK in TGF-β1-mediated EMT was investigated using gene silencing and inhibitor SB203580 and SP600125.Results The data showed that TGF-β1 induced A549 cells with alveolar epithelial type Ⅱ cell phenotype to undergo EMT.The process of EMT was accompanied by increased expression of the mesenchymal cell markers α-SMA,desmin and vimentin,and downregulation of the epithelial cell markers E-cadherin,ZO-1 and AQP-5.TGF-β1-induced EMT occurred through phosphorylation of p38 MAPK and JNK and was inhibited by inhibitor SB203580 and SP600125 and gene silencing.Conclusions Our data shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT partially via p38 MAPK and JNK activation.

关 键 词：P38丝裂原活化蛋白激酶 C-JUN氨基端激酶 肺泡上皮细胞 上皮-间质转化 转化生长因子β1 

分 类 号：R563.9[医药卫生—呼吸系统]