Changes in growth factor and cytokine mRNA levels after hepatectomy in ratwith CCl4-induced cirrhosis

Cirrhotic liver is considered to regenerate less actively than normal liver after hepatic resection. However, the mechanisms responsible for this impa ired regeneration and the cross talk of implicated factors still remain unc lear. In the present study, mRNA levels for cyclins, growth factors, and cy tokines were quantitatively assessed by a RT-PCR method at different times after hepatectomy in order to determine the relationships between these fac tors and the impaired regenerative process observed in cirrhotic liver. In our model of CCl4-induced cirrhosis, mRNA levels for cyclins and thymidine kinase provide evidence for the impaired and delayed hepatic regeneration. Moreover, we observed a significant decrease in interleukin (IL)-6 and tumo r necrosis factor-a mRNA and a significant increase for IL-1 beta mRNA. No significant change of hepatocyte growth factor (HGF) mRNA level was detecte d, contrasting with the decrease both at mRNA and protein levels in the exp ression of the c-Met/HGF receptor. Therefore, the impaired regeneration of the cirrhotic liver is associated not only with a lowered level of signals that normally promote liver growth but also with a strong decrease in c-Met receptor despite a normal expression of its specific ligand.