Differential suppression of liver-specific genes in regenerating rat liver induced by extended hepatectomy

The function of the remnant liver is critical to survival of patients following an extended hepatectomy. The aim of this study was to determine whether proliferating hepatocytes in the remnant liver preserve the expression of liver-specific genes.

Using regenerating rat livers after 30, 70, and 90% partial hepatectomy (PHx), Northern blot analyses were performed with probes for seven liver-specific genes, six growth-related genes, two housekeeping genes and two acute phase reactant protein genes.

During the regeneration after 90% PHx, the transcription of liver-specific genes showed three chronological patterns: transcription of serum albumin and cytochrome P450 2B decreased rapidly and reached a nadir at 6 to 24 h after PHx; those of apolipoprotein A-1, phosphoenolpyruvate carboxykinase and ornithine transcarbamylase decreased gradually until 24 to 48 h; those of UDP-glucuronosyltransferase and hepatocyte nuclear factor 4 did not show any changes until 48 h after PHx. In contrast, expression levels of all the growth-related genes and of housekeeping genes increased rapidly after PHx. After 30 and 70% PHx, expression of these genes changed in a similar manner to the 90% PHx case but to a lower extent.

Based upon the fractions of Ki-67 positive hepatocytes in remnant livers, we could estimate the degree of expression of each liver-specific gene in the proliferating hepatocytes. The serum albumin gene was completely suppressed, while that encoding UDP-glucuronosyltransferase was not affected. These results correlated well with the patterns of albumin and bilirubin in rat serum after PHx. Other liver-specific genes were moderately suppressed in proliferating hepatocytes. Thus, expression of liver-specific gene is differentially suppressed when hepatocytes enter a proliferation cycle. Those that are unaffected may be indispensable for maintaining the homeostasis of the living organism.