JNK信号通路调控大鼠再生肝8种细胞的增殖和凋亡  

JNK signaling pathway regulates proliferation and apoptosis of eight liver cell types during rat liver regeneration

作　　者：申亚慧[1,2] 陆琼[2] 杨彦杰[1,2] 樊晋宇[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189-197,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)

摘　　要：目的从基因转录水平了解JNK信号通路在大鼠再生肝8种细胞中的作用。方法用密度梯度离心和免疫磁珠等方法分离肝细胞(HC)、胆管上皮细胞(BEC)、卵圆细胞(OC)、肝星形细胞(HSC)、窦内皮细胞(SEC)、库普弗细胞(KC)、陷窝细胞(PC)、树突状细胞(DC)等8种肝脏细胞,用大鼠Genome 230 2.0芯片检测大鼠再生肝8种细胞的基因表达谱,用生物信息学和系统生物学等方法分析基因表达变化预示的JNK信号通路在调控大鼠再生肝8种细胞增殖、凋亡中的作用。用实时荧光定量PCR方法验证了芯片结果的可靠性。结果 JNK信号通路涉及240个基因和42条途径,其中,225个基因与大鼠肝再生相关。基因协同作用分析显示,在大鼠肝再生启动阶段,JNK信号通路启动HC和KC增殖,促进OC凋亡,启动部分PC和SEC增殖和促进部分PC和SEC凋亡;在进展阶段,JNK信号通路促进HC、BEC、KC和DC增殖,促进部分PC增殖、部分PC凋亡。在终止阶段,JNK信号通路促进HC、OC和PC凋亡,促进部分KC增殖、部分KC凋亡。结论大鼠肝再生中JNK信号通路的42条途径和225个基因参与调控大鼠再生肝8种细胞的增殖和凋亡。Objective To explore the role of JNK signaling pathway of eight liver cell types in rat liver regeneration （LR） at the gene transcription level. Methods Eight types of rat regenerating liver cells, including hepatocytes （HC）, biliary epithelial cells （BEC）, oval cells （OC）, hepatic stellate cells （HSC）, sinusoidal endothelial cells （SEC） , Kupffer cells （KC） , pit cells （PC） and dendritic cells （DC） , were isolated using the combination of percoll density gradient centrifugation and immunomagnetic bead methods. Rat Genome 230 2. 0 Array was used to detect expression profiles of JNK signaling pathway-related genes in eight liver cell types, and bioinformaties and systems biology methods were used to analyze the proliferation or apoptosis activities which were predicted by the expression profiles. RT- PCR analysis was performed to validate the reliability of the microarray results. Results Literatures showed that 42 paths and 240 genes were involved in JNK signaling pathway. Two hundred and twenty-five genes of the JNK signaling pathway were found to be involved in LR. Gene synergy analysis showed that JNK signaling pathway promoted proliferation of HC, PC, DC and KC and apoptosis of OC, PC and DC in the priming phase, enhanced proliferation of HC, BEC, KC, DC, PC and apoptosis of PC in the progressive phase, and promoted apoptosis of HC, OC, PC and KC and proliferation of KC in terminal phase. Conclusion Forty-two paths and 225 genes of JNK signaling pathway may regulate proliferation and apoptosis of the eight liver cell types during LR.

关 键 词：大鼠肝再生 JNK信号通路 再生肝8种细胞 GENOME 230 2.0芯片检测 基因协同作用 大鼠 

分 类 号：Q257[生物学—细胞生物学]