Investigation of albumin-synthesizing ability in rat cirrhotic liver-derived hepatocytes using primary hepatocyte culture

Abstract

Background/Aims: In cirrhosis, despite a decrease in the total number of hepatocytes, a normal serum albumin level is maintained during the compensatory stage of the disease in many cases. Therefore, to elucidate the mechanism in hepatocytes related to the regulation of the serum albumin level, the albumin-synthesizing ability of individual hepatocytes was investigated in cirrhotic rats. Methods: Cirrhotic rats were prepared by oral administration of furfural to male Wistar rats for 20 weeks. Albumin-synthesizing abilities of liver and of isolated hepatocyte culture were evaluated by measuring the albumin concentration in blood and culture supernatant.Expressions of albumin mRNA were compared using Northern blotting. Furthermore, transcriptional activity of the albumin gene was measured using the promoter domain of the gene. Results: The total number of hepatocytes in rat cirrhotic liver was significantly decreased compared to that in normal rat liver. However, there were no significant differences in levels of serum albumin or albumin mRNA expression between cirrhotic and normal liver. In primary hepatocyte culture, albumin mRNA expression, the amount of albumin secretion and the albumin promoter activity were clearly enhanced in cirrhotic hepatocytes compared to normal hepatocytes. Conclusion: Although the total number of hepatocytes was decreased in the rat cirrhosis models used in this study, theserum albumin level was maintained and albumin-synthesizing ability was enhanced at the transcriptional level in the individual hepatocytes. These results suggest that the maintenance of serum albumin levels in compensated cirrhosis may be due to enhancedalbumin synthesis by the hepatocytes.