Induction of immediate early genes after partial hepatectomy in cholestatic liver

The protein products of immediate early genes (IEGs) behave as transcriptional regulators and play an important role in the regulation of gene expression associated with liver cell proliferation and apoptosis. The aim of this study was to examine whether the transcription of IEGs was induced by obstructive jaundice during liver regeneration after 70% partial hepatectomy, and to examine their association with animal survival, cell proliferation, and apoptosis. Obstructive jaundice (OJ) was induced in rats by common bile duct ligation (CBDL), and 70% partial hepatectomy was performed 5 days after CBDL (OJ group). Changes in the induction of the IEGs, c-fos and c-jun, were compared between control and OJ groups in relation to survival before and after partial hepatectomy. Cell proliferation and apoptosis were evaluated by proliferating cell nuclear antigen (PCNA) immunohistological staining and by an in situ TdT-mediated d-UTP-digoxigerin nick-end labeling (TUNEL) method. The 2-week survival in the OJ group (2/7) was significantly less that of the sham operation (control) group (7/7). Enhanced induction of IEGs was evident in the OJ group after partial hepatectomy compared with findings in the control group. The PCNA-labeling index (LI) in the OJ group was increased after partial hepatectomy, but only minimally, compared with that in control animals. Apoptotic cells appeared in bile ducts and surrounding hepatocytes after partial hepatectomy in the OJ group, although apoptotic cells were rare in the control group. IEG transcription does occur after partial hepatectomy in jaundiced liver but it is enhanced and sustained, and leads to apoptosis rather than leading to the efficient proliferation of hepatocytes.