Normal liver regeneration and liver cell apoptosis after partial hepatectomy in tumor necrosis factor-α-deficient mice
Article first published online: 7 FEB 2005
Volume 25, Issue 1, pages 162–170, February 2005
How to Cite
Hayashi, H., Nagaki, M., Imose, M., Osawa, Y., Kimura, K., Takai, S., Imao, M., Naiki, T., Kato, T. and Moriwaki, H. (2005), Normal liver regeneration and liver cell apoptosis after partial hepatectomy in tumor necrosis factor-α-deficient mice. Liver International, 25: 162–170. doi: 10.1111/j.1478-3231.2005.01029.x
- Issue published online: 7 FEB 2005
- Article first published online: 7 FEB 2005
- Received 8 December 2003, accepted 14 July 2004
- nuclear factor-κB;
- proliferating cell nuclear antigen;
- transcription factor
Abstract: Aims/Background: Tumor necrosis factor-α (TNF-α) is known as a proinflammatory cytokine that has been implicated as a contributing factor in a number of disease processes. TNF-α also influences liver repair following hepatotoxic damage, and regeneration following partial hepatectomy (PH). The aim of this study was to assess the mechanism by which TNF-α influences liver cell apoptosis and regeneration following PH in TNF-α-deficient (TNF-α−/−) mice.
Methods: PH was performed in wild mice and TNF-α−/− mice.
Results: In both groups, serum alanine aminotransferase and serum total bilirubin levels comparably peaked at 6 and 48 h after PH, respectively. No differences were observed in hepatocyte proliferation, as determined by mitotic and the proliferating cell nuclear antigen labeling indices, between TNF-α+/+ and TNF-α−/− mice. Few terminal deoxynucleotidyl transferase nick end-labeling-positive hepatocytes were seen in either type of mice. Nuclear factor-κB DNA binding activity in the remaining liver of TNF-α−/− mice after PH was similar to that of control mice. Ribonuclease protection assay showed that transforming growth factor β1 mRNA was up-regulated comparably in the livers of the two groups, and that other cytokines were hardly seen in either. Interleukin-6/ signal transducer and activator of transcription-3-dependent pathway was not affected in TNF-α−/− mice.
Conclusions: These findings suggest that TNF-α has little influence on liver regeneration and liver cell apoptosis after PH in mice.