*Authors contributed equally to this study.
Analysis of bile acid-induced regulation of FXR target genes in human liver slices
Article first published online: 6 DEC 2006
Volume 27, Issue 1, pages 137–144, February 2007
How to Cite
Jung, D., Elferink, M. G. L., Stellaard, F. and Groothuis, G. M. M. (2007), Analysis of bile acid-induced regulation of FXR target genes in human liver slices. Liver International, 27: 137–144. doi: 10.1111/j.1478-3231.2006.01393.x
- Issue published online: 6 DEC 2006
- Article first published online: 6 DEC 2006
- Received 20 July 2006accepted 24 September 2006
- human in vivo system;
- nuclear receptors;
- species differences
Information about the role of nuclear receptors has rapidly increased over the last decade. However, details about their role in human are lacking. Owing to species differences, a powerful human in vitro system is needed. This study uses for the first time precision-cut human liver slices in the nuclear receptor field. The farnesoid X receptor (FXR) was chosen as a model. We were able to demonstrate that human liver slices efficiently take up bile acids and show a stable expression of a wide variety of genes relevant for bile acid metabolism, including bile acid transporters, cytochrome P450 enzymes and transcription factors. Treatment with chenodeoxycholate induced small heterodimer partner, bile salt export pump and p-glycoprotein, ABCB4 and repressed cholesterol 7α hydroxylase, hepatocyte nuclear factor (HNF)1, HNF4 and organic anion transporting peptide (OATP)1B1. OATP1B3, FXR, HNF3β and cytochrome P450 enzyme remained relatively constant. In contrast to what has been observed in mice and rat studies, SHP induction did not result in repression of sodium-dependent bile acid cotransporter expression. Further, regulation of genes seemed to be dependent on concentration and time. Taken together, the study shows that the use of liver slices is a powerful technique that enables to study nuclear receptors in the human liver.