the genetic regulation of the terminating phase of liver regeneration的基因调控肝脏再生的终止阶段.pdfVIP

Nygård et al. Comparative Hepatology 2012, 11:3 /content/11/1/3 RESEARCH Open Access The genetic regulation of the terminating phase of liver regeneration 1* 1 2 2 3 2 Ingvild E Nygård , Kim E Mortensen , Jakob Hedegaard , Lene N Conley , Trine Kalstad , Christian Bendixen and Arthur Revhaug3 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.