Wistuba, Wolfgang and Gnewuch, Carsten and Liebisch, Gerhard and Schmitz, Gerd and Langmann, Thomas (2007) Lithocholic acid induction of the FGF19 promoter in intestinal cells is mediated by PXR. WORLD JOURNAL OF GASTROENTEROLOGY, 13 (31). pp. 4230-4235. ISSN 1007-9327,
Full text not available from this repository. (Request a copy)Abstract
AIM: To study the effect of the toxic secondary bile acid lithocholic acid (LCA) on the expression of fibroblast growth factor 19 (FGF19) in intestinal cells and to characterize the pregnane-X-receptor (PXR) response of the FGF19 promoter region. METHODS: The intestinal cell line LS174T was stimulated with various concentrations of chenodeoxycholic acid and lithocholic acid for several time points. FGF19 mRNA levels were determined with quantitative realtime RT-PCR. FGF19 deletion promoter constructs were generated and the LCA response was analzyed in reporter assays. Co-transfections with PXR and RXR were carried out to study FGF19 regulation by these factors. RESULTS: LCA and CDCA strongly up-regulate FGF19 mRNA expression in LS174T cells in a time and dose dependent manner. Using reporter gene assays with several deletion constructs we found that the LCA responsive element in the human FGF19 promoter maps to the proximal regulatory region containing two potential binding sites for PXR. Overexpression of PXR and its dimerization partner retinoid X receptor (RXR) and stimulation with LCA or the potent PXR ligand rifampicin leads to a significant induction of FGF19 promoter activity in intestinal cells. CONCLUSION: LCA induced feedback inhibition of bile acid synthesis in the liver is likely to be regulated by PXR inducing intestinal FGF19 expression. 2007 WJG. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PREGNANE-X-RECEPTOR; INFLAMMATORY-BOWEL-DISEASE; ORPHAN NUCLEAR RECEPTOR; BILE-ACIDS; XENOBIOTIC METABOLISM; GENE-EXPRESSION; IDENTIFICATION; CASCADE; FXR; DETOXIFICATION; pregnane X receptor; detoxification; fibroblast growth factor 19; lithocholic acid |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Dec 2020 13:58 |
| Last Modified: | 01 Dec 2020 13:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32378 |
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