The online version of this article (doi:10.1186/1476-5926-11-3) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
IEN authored the study protocol, performed all surgical experiments, interpreted all results drafted and revised the manuscript. KEM has made substantial contribution in conduction of the liver surgery and has been involved in revising the manuscript for important intellectual content. JH, LNC and CB was responsible for all aspects of the microarray analysis, performed the statistical analysis and have been involved in drafting the manuscript. TK carried out the cytokine analysis. AR conceived of the study, participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.
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.
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.
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.
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- The genetic regulation of the terminating phase of liver regeneration
Ingvild E Nygård
Kim E Mortensen
Lene N Conley
- BioMed Central
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