Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Dec 14, 2008; 14(46): 7093-7100
Published online Dec 14, 2008. doi: 10.3748/wjg.14.7093
Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration
Jan-Peter Sowa, Jan Best, Tamas Benko, Maximillian Bockhorn, Yanli Gu, Eva-Maria Niehues, Agnieska Bucchi, Eva-Maria Benedetto-Castro, Guido Gerken, Ursula Rauen, Jörg Friedrich Schlaak
Jan-Peter Sowa, Jan Best, Eva-Maria Niehues, Agnieska Bucchi, Eva-Maria Benedetto-Castro, Guido Gerken, Jörg Friedrich Schlaak, Department of Gastroenterology and Hepatology, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany
Maximillian Bockhorn, Yanli Gu, Department of General, Visceral and Transplantation Surgery, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany
Ursula Rauen, Institute for Physiological Chemistry, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany
Tamas Benko, Department of Surgery and Transplantation, Semmelweis University, Baross u. 23, H-1082, Budapest, Hungary
Author contributions: Sowa JP, Best J, Benko T, and Schlaak JF designed the research; Sowa JP, Best J, Benko T, Bucchi A, Gu Y, Niehues EM, Benedetto-Castro EM performed the research; Bockhorn M, Rauen U contributed surgical equipment and expertise; Gerken G provided materials and laboratory equipment; Sowa JP and Schlaak JF analyzed the data; Sowa JP and Schlaak JF wrote the paper.
Supported by DFG SCHL 6-1
Correspondence to: Jörg Friedrich Schlaak, MD, Professor of Medicine, Department of Gastroenterology and Hepatology, University Hospital of Essen, Hufelandstr. 55, 45122 Essen, Germany. joerg.schlaak@uni-due.de
Telephone: +49-201-7232518 Fax: +49-201-7235749
Received: August 27, 2008
Revised: October 1, 2008
Accepted: October 8, 2008
Published online: December 14, 2008
Abstract

AIM: To investigate the molecular events involved in liver regeneration following subtotal hepatectomy (SH) as previous studies have largely focused on partial hepatectomy (PH).

METHODS: Male Wistar rats were subjected to 70% PH or 90% SH, respectively, and sacrificed at different times after surgery. Untreated and sham-operated animals served as controls. Serum and liver samples were obtained to investigate liver function, apoptosis (TUNEL assay) and transcription factors (NF-κB, Stat3; ELISA) or cytokines (HGF, TNF-α, IL-6, TGF-α, TGF-β; quantitative RT-PCR) involved in liver regeneration.

RESULTS: Serum levels of ALT and AST in animals with 70% PH differed significantly from sham-operated and control animals. We found that the peak concentration 12 h after surgery returned to control levels 7 d after surgery. LDH was increased only at 12 h after 70% PH compared to sham. Bilirubin showed no differences between the sham and 70% resection. After PH, early NF-κB activation was detected 12 h after surgery (313.21 ± 17.22 ng/mL), while there was no activation after SH (125.22 ± 44.36 ng/mL) compared to controls (111.43 ± 32.68 ng/mL) at this time point. In SH, however, NF-κB activation was delayed until 24 h (475.56 ± 144.29 ng/mL). Stat3 activation was similar in both groups. These findings correlated with suppressed and delayed induction of regenerative genes after SH (i.e. TNF-α 24 h postoperatively: 2375 ± 1220 in 70% and 88 ± 31 in 90%; IL-6 12 h postoperatively: 2547 ± 441 in 70% and 173 ± 82 in 90%). TUNEL staining revealed elevated apoptosis rates in SH (0.44% at 24 h; 0.63% at 7 d) compared to PH (0.27% at 24 h; 0.15% at 7 d).

CONCLUSION: The molecular events involved in liver regeneration are significantly influenced by the extent of resection as SH leads to suppression and delay of liver regeneration compared to PH, which is associated with delayed activation of NF-κB and suppression of proregenerative cytokines.

Keywords: Apoptosis, Cytokines, Liver regeneration, Major hepatectomy