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Open Access Research

The genetic regulation of the terminating phase of liver regeneration

Ingvild E Nygård1*, Kim E Mortensen1, Jakob Hedegaard2, Lene N Conley2, Trine Kalstad3, Christian Bendixen2 and Arthur Revhaug3

Author Affiliations

1 Department of Digestive Surgery, University Hospital of Northern-Norway, Tromsø 9038, Norway

2 Department of Genetics and Biotechnology, Faculty of Agricultural Sciences, University of Aarhus, Tjele, DK-8830, Denmark

3 Laboratory of Surgical Research, Institute of Clinical Medicine, University of Tromsø, Tromsø, 9037, Norway

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Comparative Hepatology 2012, 11:3  doi:10.1186/1476-5926-11-3

Published: 20 November 2012

Abstract

Background

After partial hepatectomy (PHx), the liver regeneration process terminates when the normal liver-mass/body-weight ratio of 2.5% has been re-established. To investigate the genetic regulation of the terminating phase of liver regeneration, we performed a 60% PHx in a porcine model. Liver biopsies were taken at the time of resection, after three weeks and upon termination the sixth week. Gene expression profiles were obtained using porcine oligonucleotide microarrays. Our study reveals the interactions between genes regulating the cell cycle, apoptosis and angiogenesis, and the role of Transforming Growth Factor-β (TGF-β) signalling towards the end of liver regeneration.

Results

Microarray analysis revealed a dominance of genes regulating apoptosis towards the end of regeneration. Caspase Recruitment Domain-Containing Protein 11 (CARD11) was up-regulated six weeks after PHx, suggesting the involvement of the caspase system at this time. Zinc Finger Protein (ZNF490) gene, with a potential negative effect on cell cycle progression, was only up-regulated at three and six weeks after PHx indicating a central role at this time. TGF-β regulation was not found to be significantly affected in the terminating phase of liver regeneration. Vasohibin 2 (VASH2) was down-regulated towards the end of regeneration, and may indicate a role in preventing a continued vascularization process.

Conclusions

CARD11, ZNF490 and VASH2 are differentially expressed in the termination phase of liver regeneration. The lack of TGF-β up-regulation suggests that signalling by TGF-β is not required for termination of liver regeneration.

Keywords:
Angiogenesis; Apoptosis; Cell cycle; Microarray analysis; Partial hepatectomy; Porcine genes