The DOI matches its Crossref record; 304 of the 304 references it cites were found in a registry or an index.
Nuclear receptors as therapeutic targets in cholestatic liver diseases
Open accessAbstract
Cholestasis results in intrahepatic accumulation of cytotoxic bile acids, which cause liver damage ultimately leading to biliary fibrosis and cirrhosis. Cholestatic liver injury is counteracted by a variety of adaptive hepatoprotective mechanisms including alterations in bile acid transport, synthesis and detoxification. The underlying molecular mechanisms are mediated mainly at a transcriptional level via a complex network involving nuclear receptors including the farnesoid X receptor, pregnane X receptor, vitamin D receptor and constitutive androstane receptor, which target overlapping, although not identical, sets of genes. Because the intrinsic adaptive response to bile acids cannot fully prevent liver injury in cholestasis, therapeutic targeting of these receptors via specific and potent agonists may further enhance the hepatic defence against toxic bile acids. Activation of these receptors results in repression of bile acid synthesis, induction of phases I and II bile acid hydroxylation and conjugation and stimulation of alternative bile acid export while limiting hepatocellular bile acid import. Furthermore, the use of nuclear receptor ligands may not only influence bile acid transport and metabolism but may also directly target hepatic fibrogenesis and inflammation. Many drugs already used to treat cholestasis and its complications such as pruritus (e.g. ursodeoxycholic acid, rifampicin, fibrates) may act via activation of nuclear receptors. More specific and potent nuclear receptor ligands are currently being developed. This article will review the current knowledge on nuclear receptors and their potential role in the treatment of cholestatic liver diseases.
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In the citing paper
“Nuclear receptors are ligand-activated transcription factors that regulate gene expression of a variety of key molecular signals involved in liver fibrosis.”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [25]
In the citing paper
“All NRs share a common structure which allows them to bind directly to DNA and regulate gene transcription.[25]”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [25]
In the citing paper
“NRs in general, play a pivotal role in the overall control of several biological processes and represent a promising target in liver diseases.[25]”
From Nuclear receptors in liver fibrosis (2021) · cites this paper as [25]
In the citing paper
“In addition to FXR also other NRs such as the pregnane X receptor (PXR/NR1I2), the constitutive androstane receptor (CAR/NR1I3) and the vitamin D receptor (NR1I1) are activated via certain BAs.45”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [45]
In the citing paper
“pharmacological activation of FXR restores BA homoeostasis by stimulation of transcription of the bile salt export pump that mediates the rate-limiting step in hepatocellular BA excretion across the canalicular membrane. Together with a reduction of BA uptake systems Na +- taurocholate cotransporting polypeptide (NTCP) and synthesis (CYP7A1) as well as stimulation of alternative basolateral export”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [45]
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Citations
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Cited by
Sorted by citations
Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis
Jia, W., Xie, G., & Jia, W. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.119 · Cited by 1,924
Bile acid signaling in metabolic disease and drug therapy
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New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond
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Self-citationNovel therapeutic targets for cholestatic and fatty liver disease
Trauner, M., & Fuchs, C. D. (2022) · Gut · doi:10.1136/gutjnl-2021-324305 · Cited by 204
Self-citationThe challenges of primary biliary cholangitis: What is new and what needs to be done
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Self-citation
Metadata
- Authors
- Zollner, G., & Trauner, M.
- Affiliations
- Medical University of Graz (AT)
- Corresponding author
- Trauner, Michael
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2008-12-24
- Volume
- 156
- Issue
- 1
- Pages
- 7-27
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC2697779
- OpenAlex
- W2022838513
- Cited by
- 146
- References
- 304
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 6 · 2023: 4 · 2022: 11 · 2021: 4 · 2020: 7 · 2019: 7 · 2018: 6 · 2017: 6 · 2016: 11 · 2015: 7 · 2014: 14 · 2013: 12 · 2012: 9
- FWCI
- 1.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Keywords
- nuclear receptors, cholestasis, cholestatic liver injury, farnesoid X receptor, pregnane X receptor, vitamin D receptor, constitutive androstane receptor, bile acid metabolism, bile acid transport, bile acid detoxification, hepatoprotection, liver fibrosis, liver cirrhosis, nuclear receptor agonists, ursodeoxycholic acid, pruritus, liver inflammation
- MeSH terms
- Bile Acids and Salts, Cholestasis, Chronic Disease, Humans, Ligands, Liver, Liver Cirrhosis, Receptors, Cytoplasmic and Nuclear
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