A microarray analysis of early activated pathways in concanavalin A-induced hepatitis  

作　　者：Qing-yi CAO Feng CHEN Jie LI Shan-shan WU Jing WANG Zhi CHEN 

机构地区：[1]State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, School ofl Medicine, Zhejiang University, Hangzhou 310003, China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2010年第5期366-377,共12页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：Project supported by the National Natural Science Foundation of China (No 30771918);the National Basic Research Program (973) of China (No 2007CB512905);the State S & T Projects (11th Five Year) (No 2008ZX10002-007) of China

摘　　要：Objective:To explore the mechanisms of fulminant hepatitis(FH) in the early stages,and to determine the critical pathways in its initiation and progression.Methods:Twelve BALB/c mice were divided into four groups:one group left as negative control and sacrificed immediately after injection of phosphate-buffered saline(PBS),and another three groups with concanavalin A(Con A) administration sacrificed at 1,3,and 6 h after injection.Affymetrix GeneChip Mouse 430 2.0 Array was employed to evaluate the expression profile of each of the 12 samples.Further analysis was done on the microarray data to extract the genes that were differentially expressed.Enrichment analysis was carried out to determine relevant pathways within which regulated genes were significantly enriched.Results:A total of 393,8354 and 11 344 differentially expressed genes were found,respectively,at three time points.During 0-1 h and 1-3 h,most of the pathways enriched with regulated genes were related to immune response and inflammation,among which Toll-like receptor(TLR) signaling and mitogen-activated protein kinase(MAPK) signaling appeared during both phases,while cytokine-cytokine receptor interaction,apoptosis,T cell receptor signaling,and natural killer(NK) cell-mediated cytotoxicity pathways emerged during the second phase.Pathways found to be significant during 3-6 h were mostly related to metabolic processes.Conclusion:The TLR signaling pathway dominates the early responses of Con A-induced FH in mice.It stimulates the production of type I cytokines,therefore recruiting and activating T/NK cells.Activated T/NK cells exert their cytotoxicity on hepatocytes through inducing death receptorintermediated apoptosis,resulting in liver injury.Objective：To explore the mechanisms of fulminant hepatitis（FH） in the early stages,and to determine the critical pathways in its initiation and progression.Methods：Twelve BALB/c mice were divided into four groups：one group left as negative control and sacrificed immediately after injection of phosphate-buffered saline（PBS）,and another three groups with concanavalin A（Con A） administration sacrificed at 1,3,and 6 h after injection.Affymetrix GeneChip Mouse 430 2.0 Array was employed to evaluate the expression profile of each of the 12 samples.Further analysis was done on the microarray data to extract the genes that were differentially expressed.Enrichment analysis was carried out to determine relevant pathways within which regulated genes were significantly enriched.Results：A total of 393,8354 and 11 344 differentially expressed genes were found,respectively,at three time points.During 0-1 h and 1-3 h,most of the pathways enriched with regulated genes were related to immune response and inflammation,among which Toll-like receptor（TLR） signaling and mitogen-activated protein kinase（MAPK） signaling appeared during both phases,while cytokine-cytokine receptor interaction,apoptosis,T cell receptor signaling,and natural killer（NK） cell-mediated cytotoxicity pathways emerged during the second phase.Pathways found to be significant during 3-6 h were mostly related to metabolic processes.Conclusion：The TLR signaling pathway dominates the early responses of Con A-induced FH in mice.It stimulates the production of type I cytokines,therefore recruiting and activating T/NK cells.Activated T/NK cells exert their cytotoxicity on hepatocytes through inducing death receptorintermediated apoptosis,resulting in liver injury.

关 键 词：Concanavalin A Fulminant hepatitis Microarray Expression profile Pathway analysis 

分 类 号：R51[医药卫生—内科学] R392[医药卫生—临床医学]