Gene expression differences of regenerating rat liver in a short interval successive partial hepatectomy

Abstract

Aim: To identify the genes expressed differentially in the regenerating rat liver in a short interval successive partial hepatectomy (SISPH), and to analyze their expression profiles.

Methods: Five hundred and fifty-one elements selected from subtractive cDNA libraries were conformed to a cDNA microarray (cDNA chip). An extensive gene expression analysis following 0-36-72-96-144 h SISPH was performed by microarray.

Results: Two hundred and sixteen elements were identified either up- or down-regulated more than 2-fold at one or more time points of SISPH. By cluster analysis and generalization analysis, 8 kinds of ramose gene expression clusters were generated in the SISPH. Of the 216 elements, 111 were up-regulated and 105 down-regulated. Except 99 unreported genes, 117 reported genes were categorized into 22 groups based on their biological functions. Comparison of the gene expression in SISPH with that after partial hepatectomy (PH) disclosed that 56 genes were specially altered in SISPH, and 160 genes were simultaneously up-regulated or down-regulated in SISPH and after PH, but in various amount and at different time points.

Conclusion: Genes expressed consistently are far less than that intermittently; the genes strikingly increased are much less than that increased only 2-5 fold; the expression trends of most genes in SISPH and in PH are similar, but the expression of 56 genes is specifically altered in SISPH. Microarray combined with suppressive subtractive hybridization can in a large scale effectively identify the genes related to liver regeneration.

Figure 1

Gene expression differences in the regenerating rat liver of 0-36-72-96-144 h SISPH.

Figure 2

Expression level of genes in the regenerating rat liver of 0-36-72-96-144 h SISPH.

Figure 3

Cluster analysis of 216 elements. A: The difference of their intensity was identified more than two-fold at least at one time point. B: A hierarchical clustering of five time points indicated that the genes at these time points hardly had a common expression profile.

Figure 4

Cluster analysis of gene expression profiles identified by cDNA microarray. These genes were classified into 8 clusters by the κ-means method.

Figure 5

Category of the 216 elements. Based on the results of the cluster analysis, eight distinct temporal patterns were designated. A: Immediate induction, B: Middle induction, C: Late induction, D: Consistent induction, E: Immediate suppression, F: Middle suppression, G: Late suppression, H: Consistent suppression.