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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].

References

  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].