Metabolic Consequences of TGFb Stimulation in CulturedPrimary Mouse Hepatocytes Screened from Transcript Data with ModeScore�


Abstract: TGFβ signaling plays a major role in the reorganization of liver tissue upon injury
and is an important driver of chronic liver disease. This is achieved by a deep impact on a
cohort of cellular functions. To comprehensively assess the full range of affected metabolic
functions, transcript changes of cultured mouse hepatocytes were analyzed with a novel
method (ModeScore), which predicts the activity of metabolic functions by scoring
transcript expression changes with 987 reference flux distributions, which yielded the
following hypotheses. TGFβ multiplies down-regulation of most metabolic functions
occurring in culture stressed controls. This is especially pronounced for tyrosine degradation,
urea synthesis, glucuronization capacity, and cholesterol synthesis. Ethanol degradation
and creatine synthesis are down-regulated only in TGFβ treated hepatocytes, but not in the
control. Among the few TGFβ dependently up-regulated functions, synthesis of various
collagens is most pronounced. Further interesting findings include: down-regulation of
glucose export is postponed by TGFβ, TGFβ up-regulates the synthesis capacity of ketone
bodies only as an early response, TGFβ suppresses the strong up-regulation of Vanin, and
TGFβ induces re-formation of ceramides and sphingomyelin.


Projects: A1.1: Central liver metabolism and its regulation under nutritional chal..., B2.3: Effect of hepatic stellate cells on hepatocyte polarity and transd...

Metabolites 2(4) : 983
1st Dec 2012

Andreas Hoppe, Iryna Ilkavets, Steven Dooley, Hermann-Georg Holzhütter

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[Andreas Hoppe] [Iryna Ilkavets] [Steven Dooley] [Hermann-Georg Holzhütter]

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Views: 2795
  • Created: 28th Nov 2012 at 12:21
  • Last updated: 24th Oct 2013 at 16:15

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