Strain specific differences in the effects of TGF-beta on hepatocyte viability and CYP450 activity in mice

Primary hepatocytes represent a widely used experimental system in the field of toxicology research and drug studies. In this study, we compared hepatocytes from mouse inbred strains C57/BL6 and DBA/2J. These two lines are the parental strains of the BXD recombinant inbred strain panel. We performed a detailed comparison of isolated hepatocytes of the two strains for susceptibility to transforming growth factor (TGF)-beta exposure and induced effects. We detected strain specific differences upon TGF-beta exposure, namely a significant decrease in the viable cell number within five days of culture and an earlier onset of dedifferentiation in DBA/2J as compared to C57/BL6 hepatocytes. In addition, the analysis of the central carbon metabolism of both strains upon TGF-beta exposure and control conditions revealed no significant differences between the hepatocytes of both strains. Therefore, in contrast to the analyzed liver-specific functions, the central carbon metabolism appears to be robust against TGF-beta exposure. The presented results provide detailed insight into strain specific differences and thereby valuable information for the selection of strains for studies such as clinically relevant fibrosis mechanisms, drug metabolism and toxicity as well as studies dealing with the analysis of TGF-beta signaling.