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TGFβ on hepatocytes

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 ModeScore yielding 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.
(A) Regulation of the degradation cascade of phenylalanine and tyrosine; (B) Regulation of selected collagens and a promoter. Red bars indicate down-regulation and green bars indicate up-regulation. Either 2 time points in the control experiment (e.g., C1h/24 h) or the same time point of control vs. TGFβ treated sample (e.g., C/T 24 h) are compared. Error bars indicate average standard deviation of 3 independent experiments. P-values refer to the probability that there is equal expression of two respective probe values, as determined with the Welch's t test

The results of the ModeScore analysis has been published [1], see also [this poster].


  1. Hoppe A, Ilkavets I, Dooley S, Holzhütter HG. (2012) Metabolic consequences of the cultivation of primary mouse hepatocytes and the effect of TGFβ stimulation screened from transcript data. Metabolites, 2012; 2(4): 983-1003. [doi, pdf].