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Analysis of the expressed genes in the regenerating rat liver after partial hepatectomy

常翠芳  袁金云  李文强  韩鸿鹏  杨柯金  赵利峰  李玉昌  张会勇  章静波  徐存拴  Salman Rahman  
【摘要】:正 It was confirmed that lots of genes participating in liver regeneration (Fukuhara et al., 2003; Yang et al., 1999). Learning gene expression patterns in liver regeneration may help to reveal how liver regeneration is initiated and controlled as well as how liver disease is leaded. In the present study, 576 elements from 4687 ESTs in the subtracted cDNA libraries were made into an in-house cDNA micro array to analyze gene expression profiles of the regenerating rat liver after PH. Hybridized with RNA from four rat livers at each time point (taken at 0, 2,4, 8,12, 16, 24, 36, 48, 72, 96 and 144h after PH), 300 elements are discovered up- or down-regulated more than two folds at one or more time points after PH. The sequence analysis showed that 152 genes were unreported, and 133 genes were reported, but they were uncertain that which role they play in liver regeneration. Analyzing their expression differences in the regenerating liver at different time points after PH showed that in the priming phase of liver regeneration (LR), the expression of 34 genes was rapidly altered within 6h and then recovered gradually to control levels in 48-72h after PH. In the cell cycle progression phase of 8-36h after PH, the expression of 86 genes was altered markedly. In the terminal phase of LR over 72h after PH, the expression of 13 genes was altered distinctly. Following biochemical actions, the 133 elements were respectively involved in stress response, in glycometabolism, in fatty and stearoyl metabolism, in oxidation and reduction response, in regulation-proteins, in glycoproteins, in lipid-proteins, in nucleolar proteins, in receptors, in factors, in hemoglobins, in immunological proteins, in chaperonins, in cytoskelets, in ribosomal proteins, in marker proteins, in amino acid enzymes, in nuclearase, in proteolytic enzymes, in proteinase inhibitors, in phopshorylases, in phosphatases, in synthase, in transferases. Their action is being studied.Clustering analysis of gene expression at twelve time points after PH showed that the most similar patterns of gene expression were showed at 12 aqd 16h, 48 and 96h as well as 72 and 144h after PH, indicating that these time points share common gene expression profiles. The selected 300 elements were categorized into six distinct temporal patterns of gene expression by the method of GeneMaths: the genes of rapid induction, whibh were expressed in the immediate early phase at 2-6h after PH; the genes of early induction in the early phase of 8-16h; the genes ofmiddle induction in intermediate phase of 16-24h; the genes of early-late induction in the early-late phase of 24-36h; the genes of late induction in the late phase of 36-72h; the genes ofconsistent repression in the terminal phase of 72-144h. It was found that abundance of the 133-gene expression in the regenerating livers is quite different. 74 of which were decreased 2-10 folds; 49 increased 2-5 folds, 9 increased 5-10 folds, 3 increased over 10 folds, and the maximum over 90 foldsBriefly, in the liver regeneration after PH, the down-regulated genes were more than the up regulated; the successively altered genes were more than the rapidly transient genes; the genes induced in the early phase were much more that in the middle phase of LR, which is much more than late phase of LR; the genes expressed in high abundance are much less than that increased 2-5 folds. Their roles in LR will be further investigated.

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