The genetic regulation of the terminating phase 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.Reestablishment of liver volume after resection is probably regulated by the functional needs of the organism, as the liver regeneration process terminates when the normal liver-mass/body-weight ratio of 2.5% has been restored. A number of studies have been conducted to assess the genetic mechanisms controlling early phases of liver regeneration, mainly in rodents [1-5]. However, the mechanisms controlling the terminating phase have not been investigated to the same extent [6,7].Two distinct pathways are activated during liver regeneration, the growth factor and cytokine regulated pathways. These regenerative pathways have several checkpoints that could be feedback inhibited and thereby regulate organ size [8]. Amongst cytokines, several negative (Suppressors of Cytokine Signalling (SOCS), IL-6, Plasminogen Activating Inhibitor (PAI)) and positive regulators (Signal Transducer and Activator of Transcription proteins (STAT), Hepatocyte Growth Factor (HGF)) are reported to regulate cell growth [9-11]. Within growth factor pathways, Transforming Growth facto