Nuclear receptors as therapeutic targets in liver disease: are we there yet?
Open accessAbstract
Nuclear receptors (NR) are ligand-modulated transcription factors that play diverse roles in cell differentiation, development, proliferation, and metabolism and are associated with numerous liver pathologies such as cancer, steatosis, inflammation, fibrosis, cholestasis, and xenobiotic/drug-induced liver injury. The network of target proteins associated with NRs is extremely complex, comprising coregulators, small noncoding microRNAs, and long noncoding RNAs. The importance of NRs as targets of liver disease is exemplified by the number of NR ligands that are currently used in the clinics or in clinical trials with promising results. Understanding the regulation by NR during pathophysiological conditions, and identifying ligands for orphan NR, points to a potential therapeutic approach for patients with liver diseases. An overview of complex NR metabolic networks and their pharmacological implications in liver disease is presented here.
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Nuclear receptors typically induce transcriptional programmes involved in metabolism or transport of the ligand, providing a feedback mechanism to maintain cellular homeostasis.
“NRs typically induce transcriptional programmes involved in metabolism or transport of the ligand, thus providing a feedback mechanism to maintain cellular homoeostasis.23 27”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [27]
Cytoskeletal alterations with formation of Mallory-Denk bodies in response to fatty acid and bile acid-induced cell stress are observed in both NASH and cholestasis.
“Another interesting convergence point are cytoskeletal alterations with formation of Mallory-Denk bodies in response to (FA and BA-induced) cell stress observed in both NASH and cholestasis.27”
From Novel therapeutic targets for cholestatic and fatty liver disease (2022) · cites this paper as [27]
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References 146 · Cited by 87
- Authors
- Rudraiah, S., Zhang, X., & Wang, L.
- Affiliations
- University of Connecticut (US)
- Corresponding author
- Rudraiah, Swetha
- Zhang, Xi
- Venue
- Annual Review of Pharmacology and Toxicology
- Publisher
- Annual Reviews
- Published
- 2016-01-06
- Volume
- 56
- Issue
- 1
- Pages
- 605-626
- ISSN
- 0362-1642 (ISSN-L)
- 1545-4304
- PMC
- PMC4919666
- OpenAlex
- W1962046992
- Cited by
- 87
- References
- 146
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 9 · 2023: 8 · 2022: 11 · 2021: 10 · 2020: 11 · 2019: 8 · 2018: 4 · 2017: 8 · 2016: 8
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Annual Review of Pharmacology and Toxicology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (I01 BX002634)
- National Institutes of Health (1I01BX002634, VA999999)
- National Institute on Alcohol Abuse and Alcoholism (R21AA024935, R21AA022482)
- National Cancer Institute (R21CA191507)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK080440, R01DK104656)
- National Institute of Environmental Health Sciences (R01ES025909)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nuclear Receptors and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Keywords
- nuclear receptors, liver disease, therapeutic target, orphan nuclear receptor, coregulators, microRNA, long non-coding RNA, hepatocellular carcinoma, hepatic steatosis, liver fibrosis, cholestasis, drug-induced liver injury, metabolic networks
- MeSH terms
- Animals, Humans, Ligands, Liver, Liver Diseases, Receptors, Cytoplasmic and Nuclear
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