Relationship And Significance Of Gene Transcription Profiles In Rat Acute Hepatic Failure Occurrence And Rat Liver Regeneration

The liver has important functions of physiology and regeneration. Acute hepatic failure (AHF) is a kind of rapid liver cell necrosis or severe impairment of liver function which was induced by pathogenic factors. To explore AHF in term of genomics and the relevance of rat liver regeneration (LR) to AHF, and the role of JNK and ERK1/2 signaling pathways of hepatocytes in rat LR and AHF. Rat Genome 230 2.0 Array was used to detect their gene expression profiles in this study, and the reliability of the detection results was confirmed by real-time polymerase chain reaction (RT-PCR). It was found that 1022 genes, including 634 up-regulated, 382 down-regulated, and 6 up/down-regulated genes, were related to occurrence of AHF. In detail, 131 genes significantly expressed at 3h, 302 at 6h, 350 at 12h, 539 at 24h, 349 at 48h, and 177 at 72h. Bioinformatics and systems biology methods were applied to analyze the correlation between gene expression changes and AHF occurrence, and it was found that a total of 23 physiological activities, including stimulus respons, inflammation response and immune response, signal transduction, transcription, transport, metabolism of carbohydrate, lipid, protein, amino acid, nucleic acid, organic acid and toxicant, oxidation reduction, homeostasis, cell proliferation, growth, differentiation and development, cellular organization, cellular apoptosis, migration and adhesion etc. were associated with AHF occurrence. 8 physiological activities including transcription, metabolisms of carbohydrate and lipid, homeostasis, cell proliferation and migration, cellular organization were increased in AHF occurrence, while 6 physiological activities including signal transduction, metabolisms of nucleic acid, organic acid and toxicant, oxidation reduction, cell adhesion etc. were decreased. Cell differentiation and development, inflammation response etc. were increased at the fore period of AHF occurrence, but decreased at its late period. It was concluded that AHF occurrence was closely related to 1022 genes and 23 physiological activities. It was found that 1022 genes were significantly changed in AHF occurrence and 948 genes in LR. Of them, 626 genes were the AHF-specific genes, 552 genes were the LR-specific and 396 genes were common genes. Analysis of hierarchical cluster showed that physiological activities of AHF and those of LR had no time correlation. Analysis of K-means cluster told that gene expression trends of C1 group in AHF and those in LR were extremely similar, that those of their C2 group were contrary, and that those of their C3, C4 and C5 groups were also similar with the gene expression changes of LR, but the latter more abundant. GO classifications and functional cluster analysis revealed that physical activities including injury, immune response, inflammatory reaction, cell migration and adhesion, etc. were increased both in AHF and in LR, whereas metabolic activities of material and energy were decreased. Of them, stimulus response, inflammation and regulation of apoptosis, etc. were stronger in AHF occurrence than in LR, but ion homeostasis, hormonal response, regulation of cell division and proliferation, etc. in AHF occurrence were weaken. Related papers showed that 42 pathways and 302 genes were involved in JNK signaling pathway. Of them, 240 genes were included in Rat Genome 230 2.0 Array which was used to detect expression changes of JNK signaling pathway-related genes in rat LR and AHF. Among them, 57 genes significant expression changes of 52 genes involved in LR, 20 genes in AHF, and 15 genes shared by LR and AHF. With the spectral function (Et) calculations the gene synergy showed that, the ways of 1 and 16 at 6-12h and the ways of 1-17 at 72h in LR to promote cell proliferation stronger than controls.The ways of 1-17 promoting cell proliferation at 6h in AHF and the ways of 34-35 inhibiting cell proliferation were weaker than in controls. In addition, the ways of 22-32 to promoting cell apoptosis at 6, 12, 72h of LR and 12, 24h of AHF was significantly increased compared with controls. And the other 4 kinds of pathways including 18-21 were not found to be involved in LR and AHF. While 14 paths and 165 genes were involved in ERK1/2 signaling pathway. Of them, 161 genes were included in above array, and it was found that, 46 genes significant expression changes in rat LR and AHF. Among them, 36 genes involved in LR, 24 genes in AHF, and 14 genes shared by them. The spectral function (Et) calculations the genetic synergy show that, the way of 4 promoting cell proliferation was weaker than the control at 6h in AHF. At 12h in LR, ways of 2, 8, 9 promoting cell proliferation and 11 inhibiting of cell proliferation were stronger than controls, but at the AHF 12h, ways of 11 inhibiting cell proliferation were stronger than the control. At LR 24h, the way of 13 inhibiting cell proliferation was weaker than the control. At AHF 72h, the way of 2 and 6 promoting cell proliferation were stronger than controls. At the same time, not yet found ways of 1, 3-5, 7, 10, 12 and 14 were involved in LR and AHF. Conclusion: The occurrence of AHF in rats is closely related to 1022 kinds of genes and 23 kinds of physical activities, AHF and the LR gene expression changes and physiological activities have common aspects, there are also discrepancies, 38 pathways of JNK signaling pathway and 7 pathways of ERK1/2 signaling pathway regulated the cell proliferation and apoptosis in liver regeneration and acute liver failure occurrence.