哺乳动物雷帕霉素靶蛋白信号通路相关基因对大鼠再生肝8种细胞生长过程的调节作用  

mTOR signaling pathway regulates growth of eight liver cell types during rat liver regeneration

作　　者：段丽娟[1,2] 王改平[1,2] 杨献光[1,2] 李德明[2] 徐存拴 

机构地区：[1]河南师范大学生命科学学院,河南新乡453007 [2]河南省-科技部共建细胞分化调控国家重点实验室培育基地,河南新乡453007

出　　处：《解剖学报》2012年第2期205-213,共9页Acta Anatomica Sinica

基　　金：国家973项目前期研究专项基金资助项目(2010CB534905);河南省科技攻关计划基金资助项目(112102310652)

摘　　要：目的从基因转录水平了解哺乳动物雷帕霉素靶蛋白(mTOR)信号通路对大鼠再生肝8种细胞的生长调节作用。方法在本实验室建立大鼠2/3肝切除模型,分离和鉴定再生肝8种细胞,采用大鼠Genome230 2.0芯片检测、数据处理及实时荧光定量PCR等方法,构建mTOR的信号通路网络,分析mTOR信号通路的相关基因在以上8种细胞中的表达谱,用系统生物学方法分析基因表达谱预示的细胞生长活动。结果 mTOR信号通路涉及110个基因和25条途径,99个基因含于大鼠Genome 230 2.0芯片,82个基因与大鼠肝再生相关。其中,在启动阶段,mTOR信号通路主要参与激活、促进肝细胞、陷窝细胞、库普弗细胞、树突状细胞、肝星形细胞和窦内皮细胞的生长过程;在进展阶段,mTOR信号通路明显地促进肝细胞、胆管上皮细胞、卵圆细胞、肝星形细胞、库普弗细胞、陷窝细胞和树突状细胞的生长过程;在终止阶段,mTOR信号通路的大多数途径对肝细胞、库普弗细胞和树突状细胞的生长过程的促进作用减弱,而途径25却对肝细胞、窦内皮细胞、肝星形细胞和陷窝细胞的生长过程有明显的抑制作用。结论 mTOR信号通路的25条途径和82个基因参与大鼠再生肝8种细胞的生长调控。Objective To explore the role of the mammalian target of rapamycin（mTOR） signaling pathway in eight types of hepatic cells during rat liver regeneration （LR） at the gene transcription level. Methods Based on the establishment of the rat 2/3 hepatectomy model, isolation and identification of eight liver cell types from rat regenerating liver, detection of expression profiles of above eight liver cell types by Rat Genome 230 2. 0 array, and application of quantitative real-time PCR, this study summarized and established the network of the mTOR signaling pathway, analyzed the expression profiles of mTOR signaling pathway-related genes in eight liver cell types during liver regeneration, and then applied systems biology method to analyze the physiological activities predicted by gene expression profiles. Results The mTOR signaling pathway was subdivided into 25 branches and contained a total of 110 genes. Among the 99 genes detected by arrays, 82 genes were identified as LR-related. At priming phase, mTOR signaling pathway was mainly involved in activating and promoting the growth of hepatocytes, pit cells, Kupffer cells, dendritic cells, hepatic stellate cells and sinusoidal endothelial cells. At the progressive phase, mTOR signaling pathway promoted the growth of hepatocytes, biliary epithelial eells, oval cells, hepatic stellate cells, Kupffer cells, pit cells and dendritic cells. At the terminal phase, the enhancement effect of roTOR pathway on the growth of hepatocytes, Kupffer cells and dendritic cells was remarkably reduced, but the inhibitory role of pathway 25 in the growth of hepatocytes, sinusoidal endothelial cells, hepatic stellate cells and pit cells was significantly increased. Conclusion The 25 branches and 82 genes involved in roTOR signaling pathway play a critical role in regulating the growth of eight cell types during rat liver regeneration.

关 键 词：肝再生 MTOR信号通路 8种肝细胞 GENOME 230 2.0芯片检测 实时荧光定量PCR 大鼠 

分 类 号：Q257[生物学—细胞生物学]