Nuclear receptor-mediated repression of human cholesterol 7α-hydroxylase gene transcription by bile acids
Open accessAbstract
Hydrophobic bile acids strongly repressed transcription of the human cholesterol 7alpha-hydroxylase gene (CYP7A1) in the bile acid biosynthetic pathway in the liver. Farnesoid X receptor (FXR) repressed CYP7A1/Luc reporter activity in a transfection assay in human liver-derived HepG2 cells, but not in human embryonic kidney (HEK) 293 cells. FXR-binding activity was required for bile acid repression of CYP7A1 transcription despite the fact that FXR did not bind to the CYP7A1 promoter. FXR-induced liver-specific factors must be required for mediating bile acid repression. Bile acids and FXR repressed endogenous CYP7A1 but stimulated alpha-fetoprotein transcription factor (FTF) and small heterodimer partner (SHP) mRNA expression in HepG2 cells. Feeding of rats with chenodeoxycholic acid repressed CYP7A1, induced FTF, but had no effect on SHP mRNA expression in the liver. FTF strongly repressed CYP7A1 transcription in a dose-dependent manner, and SHP further inhibited CYP7A1 in HepG2 cells, but not in HEK 293 cells. FXR only moderately stimulated SHP transcription, whereas FTF strongly inhibited SHP transcription in HepG2 cells. Results revealed that FTF was a dominant negative factor that was induced by bile acid-activated FXR to inhibit both CYP7A1 and SHP transcription. Differential regulation of FTF and SHP expression by bile acids may explain the wide variation in CYP7A1 expression and the rate of bile acid synthesis and regulation in different species.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Bile salts are toxic at high concentrations.
“BS are toxic in high concentration.”
From The ascending pathophysiology of cholestatic liver disease (2017) · cites this paper as [11]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 27 · Cited by 112
- Authors
- Chen, W., Owsley, E., Yang, Y., Stroup, D., & Chiang, J. Y. L.
- Affiliations
- Northeast Ohio Medical University (US)
- Corresponding author
- Chiang, John Y.L.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2001-09
- Volume
- 42
- Issue
- 9
- Pages
- 1402-1412
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W1862042053
- Cited by
- 112
- References
- 27
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 2 · 2012: 7
- FWCI
- 8.27
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (5r01dk044442-26, 5r01gm031584-14, DK44442)
- National Institute of General Medical Sciences (GM 31584)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK44442, R01-DK-044442, R01DK058379)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- CYP7A1, bile acids, farnesoid X receptor, transcriptional repression, small heterodimer partner, chenodeoxycholic acid, bile acid synthesis, hepatic gene regulation, dominant negative regulation
- MeSH terms
- Receptor, Farnesoid X-Activated, Animals, Bile Acids and Salts, Carrier Proteins, Cell Line, Cholesterol 7-alpha-Hydroxylase, DNA, DNA-Binding Proteins, Embryo, Mammalian, Cricetinae, Humans, Hydroxysteroid Dehydrogenases, Kidney, Liver, Luciferases, Membrane Glycoproteins, Promoter Regions, Genetic, Recombinant Fusion Proteins, RNA, Messenger, Taurocholic Acid, Transcription Factors, Transcription, Genetic, Transfection, Tumor Cells, Cultured, Gene Expression, CHO Cells, Receptors, Cytoplasmic and Nuclear, Receptors, Retinoic Acid, Caco-2 Cells, Reverse Transcriptase Polymerase Chain Reaction, 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific), Retinoid X Receptors, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
