Wnt信号通路相关分子在肝纤维化中的表达水平变化及其意义  

The gene expression and role of Wnt signal pathway in liver fibrosis

作　　者：熊伍军[1] 何益[1] 刘菲[1] 江鸣[1] 刘雁冰[1] 

机构地区：[1]上海同济大学附属东方医院消化科,200120

出　　处：《中华消化杂志》2008年第9期612-616,共5页Chinese Journal of Digestion

摘　　要：目的观察Wnt信号通路相关分子在实验性肝纤维化组织中表达水平的变化，探讨其在肝纤维化发生中的作用。方法建立大鼠肝纤维化动物模型，用Wnt信号通路PCRarray功能基因芯片观察Wnt信号通路相关分子在肝纤维化模型中表达水平的变化，以模型组较正常组表达上调或下调2倍为差异表达基因；利用免疫组化及Western印迹观察平滑肌肌动蛋白、wnt4、Frizzled2、β-钙粘蛋白在肝纤维化组织表达水平的变化。结果芯片检测发现共有36条基因发生了显著改变，模型组较正常组上调2倍的基因有25个，上调基因主要包括Wnt5a类基因，如Wnt4、Wnt5a、Wnt11等，分别上调了13．9、16．5和2．17倍；较正常组下调2倍的基因有11个，主要为Wnt1、Wnt3等，分别下调了2．32、2．15倍。免疫组化及Western印迹检测发现模型组肝组织Wnt4、Frizzled2的表达水平较正常组显著上升，而磷酸化的β-钙粘蛋白的表达水平下降。结论经典及非经典Wnt信号通路均可能参与了实验性肝纤维化的发生机制。Objective To study the gene expression of Wnt signal transduction pathway in experimental liver fibrosis and to investigate its role in liver fibrosis. Methods Liver fibrosis model was induced with carbon tetrachloride in 8 SD rats . Another 8 healthy rats were served as control. The gene expression in liver tissues of models and controls were examined using real time PCR array. The differential gene expression was identified as either up- or down regulated 2 fold. The expressions of smooth muscle actin （SMA）, Writ4, Frizzled2 and β-catenin in the tissues were examined by immunohistochemistry and Western blot. Results The examination confirmed that 36 genes were differentially expressed, including 25 genes up regulated and 11 genes down regulated. Compared with the controls, the expressions of Wnt4, WntSa and Wnt11 were up regulated more than 13.9-, 16.5 and 2. 17-fold respectively, while the expressions of Wntl and Wnt3 were down-regulated more than 2.32- and 2. 15-fold respectively in fibrotic liver. Immunohistochemistry and Western blot showed that the expressions of SMA, Writ4 and Frizzled2 in fibrotic liver were remarkably higher than those in normal controls. While the level of phosphorylated β-catenin was decreased. Conclusion Both canonical and noneanonical Wnt signal transduction pathway may involve in the mechanism of liver fibrogenesis.

关 键 词：肝硬化 衔接蛋白质类 信号转导 寡核苷酸序列分析 

分 类 号：R686[医药卫生—骨科学]