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

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

doi:10.3390/metabo2040983

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

Andreas Hoppe

^1,*,

Iryna Ilkavets

²,

Steven Dooley

² and

Hermann-Georg Holzhütter

Institute for Biochemistry, Charité University Medicine Berlin, Charitéplatz 1/Virchowweg 6, 10117 Berlin, Germany

Molecular Hepatology and Alcohol Associated Diseases, Medical Clinic II, Medical Faculty Mannheim at Heidelberg University, Theodor-Kutzer-Ufer 1-3, H42 E4, 68167 Mannheim, Germany

Author to whom correspondence should be addressed.

Metabolites 2012, 2(4), 983-1003; https://doi.org/10.3390/metabo2040983

Received: 29 August 2012 / Revised: 18 October 2012 / Accepted: 7 November 2012 / Published: 21 November 2012

(This article belongs to the Special Issue Metabolic Network Models)

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Abstract

TGFb 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. TGFb 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 TGFb treated hepatocytes, but not in the control. Among the few TGFb dependently up-regulated functions, synthesis of various collagens is most pronounced. Further interesting findings include: down-regulation of glucose export is postponed by TGFb, TGFb up-regulates the synthesis capacity of ketone bodies only as an early response, TGFb suppresses the strong up-regulation of Vanin, and TGFb induces re-formation of ceramides and sphingomyelin. View Full-Text

Keywords: hepatocyte; transforming growth factor beta; transcriptomics; metabolic network; VirtualLiver Network

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Supplementary Materials

Supplementary File 1:
Complete account of the selection process (PDF, 2112 KiB)
Supplementary File 2:
Supplemental File (ZIP, 168 KiB)
Supplementary File 3:
Definition of the simulations and solution summary (PDF, 792 KiB)
Supplementary File 4:
Solutions (PDF, 3957 KiB)
Supplementary File 5:
Scores and amplitudes tables (PDF, 994 KiB)
Supplementary File 6:
Detailed reaction scores (PDF, 617 KiB)
Supplementary File 7:
Setting of the weights (PDF, 80 KiB)

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Hoppe, A.; Ilkavets, I.; Dooley, S.; Holzhütter, H.-G. Metabolic Consequences of TGFb Stimulation in CulturedPrimary Mouse Hepatocytes Screened from Transcript Data with ModeScore . Metabolites 2012, 2, 983-1003. https://doi.org/10.3390/metabo2040983

AMA Style

Hoppe A, Ilkavets I, Dooley S, Holzhütter H-G. Metabolic Consequences of TGFb Stimulation in CulturedPrimary Mouse Hepatocytes Screened from Transcript Data with ModeScore . Metabolites. 2012; 2(4):983-1003. https://doi.org/10.3390/metabo2040983

Chicago/Turabian Style

Hoppe, Andreas, Iryna Ilkavets, Steven Dooley, and Hermann-Georg Holzhütter. 2012. "Metabolic Consequences of TGFb Stimulation in CulturedPrimary Mouse Hepatocytes Screened from Transcript Data with ModeScore " Metabolites 2, no. 4: 983-1003. https://doi.org/10.3390/metabo2040983

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

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