hHGF调控肝纤维化信号转导途径研究  

Signal transduction pathway in liver fibrosis regulated by human hepatocyte growth factor

作　　者：刘灏[1] 陈景良[1] 向国安[2] 

机构地区：[1]南方医科大学中西医结合医院普外科,广东广州510315 [2]广东省第二人民医院普外科,广东广州510317

出　　处：《南方医科大学学报》2010年第3期431-434,共4页Journal of Southern Medical University

基　　金：国家自然科学基金(30600524)

摘　　要：目的应用寡聚核苷酸基因表达谱芯片研究人肝细胞生长因子(hHGF)转染肝癌细胞系后基因表达谱的差异,分析hHGF抗肝纤维化的信号转导途径。方法应用包含20000条人类全长基因的寡聚核苷酸芯片ImaGene3.0检测hHGF转染的肝癌细胞系基因表达谱差异,并选择其中参与肝纤维化过程的存在表达上调基因[信号转导和转录激活因子1(STAT1)和丝裂原活化蛋白激酶1(MAPK1)]用RT-PCR方法进行验证分析。结果基因芯片筛选出存在差异表达的基因,其中包括转录因子、细胞周期素、细胞因子相关蛋白、糖脂类物质代谢相关酶及细胞信号转导相关因子等,RT-PCR验证参与肝纤维化过程中的几种存在表达差异的基因,其中STAT1和MAPK1表达明显上调,与基因芯片分析结果一致。结论hHGF转染肝癌细胞系存在基因表达差异,可能影响细胞周期的调控、物质代谢相关过程及细胞信号转导系统,hHGF可能通过激活JAK/STAT通路和MAPK通路发挥其抗肝纤维化作用。Objective To explore the changes in the gene expression profiles in HepG2 cells transfected by human hepatocyte growth factor （hHGF） and analyze the signal transduction pathway in liver fibrosis regulated by hHGF. Method A 20 000 gene cDNA microarray （Affymetrix） was used to examine the gene expressions in the HepG2 cells transfected by hHGF. The differentially expressed genes were identified and some genes with possible contribution to hepatic fibrosis were subjected to real-time PCR analysis. Result The differentially expressed genes were mostly transcription regulatory molecules, cytokines, signal transduction, glucose metabolism, lipid metabolism. The results of real-time PCR showed up-regulated STAT1 and MAPK1 expression in the cells as were consistent with genechip analysis results. Conclusion hHGF gene transfection results in the gene expression profile changes in HepG2 cells. HGF may regulate liver fibrosis via the JAK/STAT and MAPK pathways.

关 键 词：肝细胞生长因子 HEPG2细胞 肝纤维化 基因芯片 基因表达 

分 类 号：R575.2[医药卫生—消化系统]