Relationship and Significance of Gene Transcription Profiles in Rat Liver Regeneration and Liver Cirrhosis Occurrence
|Keywords||Liver cirrhosis Liver regeneration Gene expression profiles JNK signaling pathway ERK1/2 signaling pathway|
Liver cirrhosis (LC) is a kind of chronic、progressive and diffuse liver disease, which is pathologically characterized with abnormality and necrosis of hepatic cells, proliferation of fibrous tissue, nodular regeneration and pseudolobule formation. To explore LC in term of genome, Rat Genome 230 2.0 Array was used to detect the gene expression profiles of LC in 3W, 6W and 9W of CCl4 treatment in this study. It was found that a total of 304 genes, were related to LC occurrence. Bioinformatics and systems biology methods were applied to analyze the correlation between gene expression changes of rat normal liver cells and that of LC, showing that a total of 16 physiological activities, including responses to stimulus, inflammation and immune, signal transduction, transcription, transport, metabolisms of carbohydrate, lipid, amino acid and protein, oxidative stress, homeostasis, cell proliferation, growth, differentiation and development, cellular organization, cell apoptosis, migration and adhesion were closely associated with LC occurrence. Of them, inflammation response, cell proliferation and apoptosis were increased in LC occurrence, while immune response, signal transduction, oxidative stress, cell differentiation and development and adhesion were decreased. To explore the relevance of rat liver cirrhosis to rat liver regeneration, Rat Genome 230 2.0 Array was used to detect the gene expression abundance of them, it was found that 304 genes were changed significantly in expression in rat LC occurrence and 948 genes in rat LR. Correlation of time was analyzed by H-clustering between LC and LR. According to similarity of gene expression, a total of 1096 genes were divided into 6 kinds of groups by K-means. GO classifications and functional cluster analysis found that physiological activities including immune and inflammatory response, cell migration and adhesion were increased both in LC and in LR, whereas various metabolic activities were decreased. Among them, reaction of liver to stimulation in LC was stronger than in LR in Cluster 2, but in Cluster 6 showed a contrary result. At the same time, DNA repair, cell proliferation, lipid metabolism, homeostasis, oxidation reduction etc in LC were weaker than in LR. In order to understand the similarities and differences of JNK, ERK1/2 signaling pathways in rat liver cirrhosis and liver regeneration on the base of gene transcription, gene expression profiles were detected by Rat Genome 230 2.0 Array between them bioinformatics and system biology. Analysis showed that JNK signaling pathway involved 42 paths, of them, 37 paths regulation cell proliferation and apoptosis of rat liver regeneration, but the effects on LC is insignificant. 302 genes involved in JNK signaling pathway, Rat Genome 230 2.0 Array contains 240 genes, of them, 79 genes were changed significantly in expression, 52 genes were involved in LC, 5 genes were involved in LR, and 22 genes were shared in both. ERK1/2 signaling pathway involved 14 paths, of them, 6 paths regulated cell proliferation of rat liver regeneration and liver cirrhosis, but the effects on liver cirrhosis is insignificant. 165 genes involved in ERK1/2 signaling pathway, Rat Genome 230 2.0 Array contains 161 genes, of them, 46 genes were changed significantly in expression, 35 genes were involved in LC, 4 genes were involved in LR, and 7 genes were shared in both.