Display options
Cite
Hoppe A, Ilkavets I, Dooley S, et al. Metabolic Consequences of TGFb Stimulation in CulturedPrimary Mouse Hepatocytes Screened from Transcript Data with ModeScore . Metabolites. 2012;2(4):983-1003doi: 10.3390/metabo2040983.
Hoppe, A., Ilkavets, I., Dooley, S., & Holzhütter, H. G. (2012). Metabolic Consequences of TGFb Stimulation in CulturedPrimary Mouse Hepatocytes Screened from Transcript Data with ModeScore . Metabolites, 2(4), 983-1003. https://doi.org/10.3390/metabo2040983
Hoppe, Andreas, et al. "Metabolic Consequences of TGFb Stimulation in CulturedPrimary Mouse Hepatocytes Screened from Transcript Data with ModeScore ." Metabolites vol. 2,4 (2012): 983-1003. doi: https://doi.org/10.3390/metabo2040983
Hoppe A, Ilkavets I, Dooley S, Holzhütter HG. Metabolic Consequences of TGFb Stimulation in CulturedPrimary Mouse Hepatocytes Screened from Transcript Data with ModeScore . Metabolites. 2012 Nov 21;2(4):983-1003. doi: 10.3390/metabo2040983. PMID: 24957771; PMCID: PMC3901234.
Copy Download .nbib Format: NLM
Share it on

Metabolites. 2012 Nov 21;2(4):983-1003. doi: 10.3390/metabo2040983.

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

Metabolites

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

Affiliations

  1. Institute for Biochemistry, Charité University Medicine Berlin, Charitéplatz 1/Virchowweg 6, 10117 Berlin, Germany. [email protected].
  2. 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. [email protected].
  3. 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. [email protected].
  4. Institute for Biochemistry, Charité University Medicine Berlin, Charitéplatz 1/Virchowweg 6, 10117 Berlin, Germany. [email protected].

PMID: 24957771 PMCID: PMC3901234 DOI: 10.3390/metabo2040983

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.

References

  1. Hepatogastroenterology. 2012 Jan-Feb;59(113):235-40 - PubMed
  2. PLoS Comput Biol. 2008 May 16;4(5):e1000082 - PubMed
  3. Gastroenterology. 2008 Aug;135(2):642-59 - PubMed
  4. Nat Genet. 2000 May;25(1):25-9 - PubMed
  5. BMC Bioinformatics. 2011 Jan 22;12:28 - PubMed
  6. Biometrika. 1947;34(1-2):28-35 - PubMed
  7. In Vitro Cell Dev Biol Anim. 2011 Sep;47(8):526-34 - PubMed
  8. Genome Inform. 2006;17(1):195-207 - PubMed
  9. Biotechnol Genet Eng Rev. 2010;26:281-96 - PubMed
  10. Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17845-50 - PubMed
  11. J Biol Chem. 2003 Aug 15;278(33):31067-77 - PubMed
  12. Mol Syst Biol. 2010 Sep 7;6:411 - PubMed
  13. Mol Syst Biol. 2010 Sep 7;6:401 - PubMed
  14. Am J Physiol Endocrinol Metab. 2006 Dec;291(6):E1151-9 - PubMed
  15. J Hepatol. 2010 Mar;52(3):407-16 - PubMed
  16. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1777-82 - PubMed
  17. Novartis Found Symp. 2002;247:91-101; discussion 101-3, 119-28, 244-52 - PubMed
  18. ALTEX. 2000;17(1):3-10 - PubMed
  19. Bioprocess Biosyst Eng. 2006 Apr;28(5):331-40 - PubMed
  20. Surgery. 2010 Feb;147(2):288-94 - PubMed
  21. Free Radic Biol Med. 2006 Oct 1;41(7):1100-12 - PubMed
  22. J Nutr. 2011 Oct;141(10):1799-804 - PubMed
  23. Eur J Biochem. 2004 Jul;271(14):2905-22 - PubMed
  24. Syst Biol (Stevenage). 2006 Nov;153(6):433-47 - PubMed
  25. Yale J Biol Med. 1978 Nov-Dec;51(6):625-33 - PubMed
  26. Bioinformatics. 2004 Aug 4;20 Suppl 1:i178-85 - PubMed
  27. Methods Mol Biol. 2012;806:99-120 - PubMed
  28. Hepatology. 2009 Jun;49(6):2031-43 - PubMed
  29. Hepatology. 1999 Mar;29(3):621-3 - PubMed
  30. Nat Methods. 2009 Aug;6(8):589-92 - PubMed
  31. Am J Hematol. 1990 Apr;33(4):249-54 - PubMed
  32. Hepatology. 2000 Dec;32(6):1377-85 - PubMed
  33. Biochem Biophys Res Commun. 2012 Jan 13;417(2):653-8 - PubMed
  34. Am J Physiol Regul Integr Comp Physiol. 2007 May;292(5):R1851-61 - PubMed
  35. Nat Biotechnol. 2008 Sep;26(9):1003-10 - PubMed
  36. Int J Hepatol. 2012;2012:459278 - PubMed
  37. Metabolites. 2012 Sep 12;2(3):614-31 - PubMed
  38. Cell Tissue Res. 2012 Jan;347(1):245-56 - PubMed
  39. Bioinformatics. 2009 Dec 1;25(23):3158-65 - PubMed
  40. Nucleic Acids Res. 2008 Jan;36(Database issue):D480-4 - PubMed
  41. Matrix Biol. 2005 May;24(3):177-84 - PubMed
  42. BMC Syst Biol. 2007 Jun 01;1:23 - PubMed
  43. Am J Physiol Endocrinol Metab. 2011 Feb;300(2):E287-95 - PubMed
  44. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4229-33 - PubMed

Publication Types