Oxygen drives hepatocyte differentiation and phenotype stability in liver cell lines.

ABSTRACT: The in vitro generation of terminally differentiated hepatocytes is an unmet need. We investigated the contribution of oxygen concentration to differentiation in human liver cell lines HepaRG and C3A. HepaRG cells were cultured under hypoxia (5%O₂), normoxia (21%O₂) or hyperoxia (40%O₂). Cultures were analysed for hepatic functions, gene transcript levels, and protein expression of albumin, hepatic transcription factor CEBPα, hepatic progenitor marker SOX9, and hypoxia inducible factor (HIF)1α. C3A cells were analysed after exposure to normoxia or hyperoxia. In hyperoxic HepaRG cultures, urea cycle activity, bile acid synthesis, CytochromeP450 3A4 (CYP3A4) activity and ammonia elimination were 165-266% increased. These effects were reproduced in C3A cells.

SUBMITTER: van Wenum M 

PROVIDER: S-EPMC6039343 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature