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 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.


Projects: D4: Regeneration and Liver Size

PLoS ONE 9(4) : e93207
1st Apr 2014

Nadine Hohmann, Wei Weiwei, Uta Dahmen, Olaf Dirsch, Andreas Deutsch, Anja Voss-Böhme

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[Nadine Hohmann] [Weiwei Wei] [Uta Dahmen] [Olaf Dirsch] [Andreas Deutsch]

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Views: 2011
  • Created: 24th Apr 2014 at 14:21
  • Last updated: 24th Apr 2014 at 14:26

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