Epidermal growth factor is decreased in liver of rats with biliary cirrhosis but does not act as paracrine growth factor immediately after hepatectomy

Background/Aims: Epidermal growth factor, a potent mitogen for hepatocytes and cholangiocytes, is thought to act as an immediate-early gene after part ial hepatectomy, Since regeneration is impaired in cirrhosis, we explored t he expression of epidermal growth factor in cirrhotic rat liver immediately after partial hepatectomy, Methods: Cirrhosis was induced by bile duct ligation (n=21); sham-operated animals served as controls (n=21), Twenty-five days after initial surgery a nimals were subjected to 70% partial hepatectomy or sham operation; the liv er was sampled before surgery and 20, 40 and 90 min thereafter. Epidermal g rowth factor mRNA levels were assessed by quantitative reverse transcriptio n polymerase chain reaction, Protein expression was estimated by immunohist ochemistry using a polyclonal antibody against epidermal growth factor. Results: Before hepatectomy, epidermal growth factor mRNA averaged 70.3+/-3 9.9 pg/mu g of total RNA in controls; this was markedly decreased to 21.9+/ -12.7 pg/mu g RNA in bile duct ligation (p<0.01), Epidermal growth factor m RNA did not increase after partial hepatectomy in either group, with the ex ception of sham-operated controls. Immunohistochemistry revealed that parti al hepatectomy had no effect on epidermal growth factor expression. Hepatoc ytes showed uniformly cytosolic epidermal growth factor in controls, while in bile duct ligation immunostaining was faint or absent. Cholangiocytes ex hibited a strong cytosolic staining in all experimental groups. Conclusions: The present study shows that epidermal growth factor is reduce d in the cirrhotic liver, This could contribute to the loss of parenchymal liver tissue observed in cirrhosis. The lack of up-regulation after PH shed s doubt on the role of epidermal growth factor as an immediate-early gene i n hepatic regeneration. Further, we demonstrate that epidermal growth facto r accumulates in cholangiocytes. This observation is strong evidence for in volvement of the mitogen epidermal growth factor in the proliferation of bi le ducts during cirrhogenesis.