Expression patterns of cytokine, growth factor and cell cycle-related genes after partial hepatectomy in rats with thioacetamide-induced cirrhosis

Abstract

To examine the differences in the responses of normal and cirrhotic livers to partial hepatectomy in relation to the factors influencing liver regeneration. Cirrhosis was induced in rats by administration of thioacetamide. Untreated rats were used as controls. The control rats as well as the cirrhotic rats were subjected to 70% partial hepatectomy. At different time points after hepatectomy, the livers were collected and the levels of cytokines, growth factors and cell cycle proteins were analyzed. After hepatectomy, the cirrhotic remnant expressed significantly lower levels of cyclin D1, its kinase partner, cdk4, and cyclin E as compared to the controls up to 72 h post hepatectomy. Significantly lower levels of cyclin A and cdk2 were also observed while the cdk inhibitor, p27 was significantly higher. In addition, the cirrhotic group had lower IL-6 levels than the control group at all time points up to 72 h following resection. The data from our study shows that impaired liver regeneration in cirrhotic remnants is associated with low expression of cyclins and cdks. This might be the consequence of the low IL-6 levels in cirrhotic liver remnant which would in turn influence the actions of transcription factors that regulate genes involved in cell proliferation and metabolic homeostasis during the regeneration process.