A microarray analysis of early activated pathways in concanavalin A-induced hepatitis |
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| Authors: | Qing-yi Cao Feng Chen Jie Li Shan-shan Wu Jing Wang and Zhi Chen |
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| Institution: | (1) Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, Faculty of Medicine, Tottori University, Nishicho 86, Yonago Tottori, 683-8503, Japan;(2) First Department of Internal Medicine, School of Medicine, Iwate Medical School, Uchimaru 19-1, Morioka Iwate, 020-8505, Japan;(3) Division of Gastroenterology and Hepatology, School of Medicine, Saitama Medical University Hospital, 38 Morohongo, Moroyama-machi, Iruma-gun Saitama, 350-0495, Japan;(4) Division of Molecular and Genetic Medicine, Department of Genetic Medicine and Regenerative Therapeutics, Tottori University, Nishicho 86, Yonago Tottori, 683-8503, Japan |
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| Abstract: | 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 6h 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 11344 differentially expressed genes were found,respectively,at three time points.During 0-1h and 1-3h,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 during3-6h 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. |
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| Keywords: | Concanavalin A Fulminant hepatitis Microarray Expression profile Pathway analysis |
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