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The genetic regulation of the terminating phase of liver regeneration

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...

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Autores principales: Nygård, Ingvild E, Mortensen, Kim E, Hedegaard, Jakob, Conley, Lene N, Kalstad, Trine, Bendixen, Christian, Revhaug, Arthur
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558440/
https://www.ncbi.nlm.nih.gov/pubmed/23164283
http://dx.doi.org/10.1186/1476-5926-11-3
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author Nygård, Ingvild E
Mortensen, Kim E
Hedegaard, Jakob
Conley, Lene N
Kalstad, Trine
Bendixen, Christian
Revhaug, Arthur
author_facet Nygård, Ingvild E
Mortensen, Kim E
Hedegaard, Jakob
Conley, Lene N
Kalstad, Trine
Bendixen, Christian
Revhaug, Arthur
author_sort Nygård, Ingvild E
collection PubMed
description 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.
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spelling pubmed-35584402013-01-31 The genetic regulation of the terminating phase of liver regeneration Nygård, Ingvild E Mortensen, Kim E Hedegaard, Jakob Conley, Lene N Kalstad, Trine Bendixen, Christian Revhaug, Arthur Comp Hepatol Research 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. BioMed Central 2012-11-20 /pmc/articles/PMC3558440/ /pubmed/23164283 http://dx.doi.org/10.1186/1476-5926-11-3 Text en Copyright ©2012 Nygård et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Nygård, Ingvild E
Mortensen, Kim E
Hedegaard, Jakob
Conley, Lene N
Kalstad, Trine
Bendixen, Christian
Revhaug, Arthur
The genetic regulation of the terminating phase of liver regeneration
title The genetic regulation of the terminating phase of liver regeneration
title_full The genetic regulation of the terminating phase of liver regeneration
title_fullStr The genetic regulation of the terminating phase of liver regeneration
title_full_unstemmed The genetic regulation of the terminating phase of liver regeneration
title_short The genetic regulation of the terminating phase of liver regeneration
title_sort genetic regulation of the terminating phase of liver regeneration
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558440/
https://www.ncbi.nlm.nih.gov/pubmed/23164283
http://dx.doi.org/10.1186/1476-5926-11-3
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