Metabolic Consequences of TGFβ Stimulation in Cultured Primary Mouse Hepatocytes Screened from Transcript Data with ModeScore

Metabolites

Andreas Hoppe²  Iryna Ilkavets¹  Steven Dooley¹ 

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

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

DOI  :  10.3390/metabo2040983

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.