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How Does a Single Cell Know When the Liver Has Reached Its Correct Size?

The liver is a multi-functional organ that regulates major physiological processes and that possesses a remarkable regeneration capacity. After loss of functional liver mass the liver grows back to its original, individual size through hepatocyte proliferation and apoptosis. How does a single hepato...

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Autores principales: Hohmann, Nadine, Weiwei, Wei, Dahmen, Uta, Dirsch, Olaf, Deutsch, Andreas, Voss-Böhme, Anja
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972176/
https://www.ncbi.nlm.nih.gov/pubmed/24690888
http://dx.doi.org/10.1371/journal.pone.0093207
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author Hohmann, Nadine
Weiwei, Wei
Dahmen, Uta
Dirsch, Olaf
Deutsch, Andreas
Voss-Böhme, Anja
author_facet Hohmann, Nadine
Weiwei, Wei
Dahmen, Uta
Dirsch, Olaf
Deutsch, Andreas
Voss-Böhme, Anja
author_sort Hohmann, Nadine
collection PubMed
description The liver is a multi-functional organ that regulates major physiological processes and that possesses a remarkable regeneration capacity. After loss of functional liver mass the liver grows back to its original, individual size through hepatocyte proliferation and apoptosis. How does a single hepatocyte ‘know’ when the organ has grown to its final size? This work considers the initial growth phase of liver regeneration after partial hepatectomy in which the mass is restored. There are strong and valid arguments that the trigger of proliferation after partial hepatectomy is mediated through the portal blood flow. It remains unclear, if either or both the concentration of metabolites in the blood or the shear stress are crucial to hepatocyte proliferation and liver size control. A cell-based mathematical model is developed that helps discriminate the effects of these two potential triggers. Analysis of the mathematical model shows that a metabolic load and a hemodynamical hypothesis imply different feedback mechanisms at the cellular scale. The predictions of the developed mathematical model are compared to experimental data in rats. The assumption that hepatocytes are able to buffer the metabolic load leads to a robustness against short-term fluctuations of the trigger which can not be achieved with a purely hemodynamical trigger.
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spelling pubmed-39721762014-04-04 How Does a Single Cell Know When the Liver Has Reached Its Correct Size? Hohmann, Nadine Weiwei, Wei Dahmen, Uta Dirsch, Olaf Deutsch, Andreas Voss-Böhme, Anja PLoS One Research Article The liver is a multi-functional organ that regulates major physiological processes and that possesses a remarkable regeneration capacity. After loss of functional liver mass the liver grows back to its original, individual size through hepatocyte proliferation and apoptosis. How does a single hepatocyte ‘know’ when the organ has grown to its final size? This work considers the initial growth phase of liver regeneration after partial hepatectomy in which the mass is restored. There are strong and valid arguments that the trigger of proliferation after partial hepatectomy is mediated through the portal blood flow. It remains unclear, if either or both the concentration of metabolites in the blood or the shear stress are crucial to hepatocyte proliferation and liver size control. A cell-based mathematical model is developed that helps discriminate the effects of these two potential triggers. Analysis of the mathematical model shows that a metabolic load and a hemodynamical hypothesis imply different feedback mechanisms at the cellular scale. The predictions of the developed mathematical model are compared to experimental data in rats. The assumption that hepatocytes are able to buffer the metabolic load leads to a robustness against short-term fluctuations of the trigger which can not be achieved with a purely hemodynamical trigger. Public Library of Science 2014-04-01 /pmc/articles/PMC3972176/ /pubmed/24690888 http://dx.doi.org/10.1371/journal.pone.0093207 Text en © 2014 Hohmann et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Hohmann, Nadine
Weiwei, Wei
Dahmen, Uta
Dirsch, Olaf
Deutsch, Andreas
Voss-Böhme, Anja
How Does a Single Cell Know When the Liver Has Reached Its Correct Size?
title How Does a Single Cell Know When the Liver Has Reached Its Correct Size?
title_full How Does a Single Cell Know When the Liver Has Reached Its Correct Size?
title_fullStr How Does a Single Cell Know When the Liver Has Reached Its Correct Size?
title_full_unstemmed How Does a Single Cell Know When the Liver Has Reached Its Correct Size?
title_short How Does a Single Cell Know When the Liver Has Reached Its Correct Size?
title_sort how does a single cell know when the liver has reached its correct size?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972176/
https://www.ncbi.nlm.nih.gov/pubmed/24690888
http://dx.doi.org/10.1371/journal.pone.0093207
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