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Nuclear receptors : pathophysiological mechanisms and drug targets in liver disease

(2024) GUT. 73(9). p.1562-1569
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Abstract
Nuclear receptors (NRs) are ligand-dependent transcription factors required for liver development and function. As a consequence, NRs have emerged as attractive drug targets in a wide range of liver diseases. However, liver dysfunction and failure are linked to loss of hepatocyte identity characterised by deficient NR expression and activities. This might at least partly explain why several pharmacological NR modulators have proven insufficiently efficient to improve liver functionality in advanced stages of diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). In this perspective, we review the most recent advances in the hepatic NR field and discuss the contribution of multiomic approaches to our understanding of their role in the molecular organisation of an intricated transcriptional regulatory network, as well as in liver intercellular dialogues and interorgan cross-talks. We discuss the potential benefit of novel therapeutic approaches simultaneously targeting multiple NRs, which would not only reactivate the hepatic NR network and restore hepatocyte identity but also impact intercellular and interorgan interplays whose importance to control liver functions is further defined. Finally, we highlight the need of considering individual parameters such as sex and disease stage in the development of NR-based clinical strategies.
Keywords
LIVER FAILURE, NONALCOHOLIC STEATOHEPATITIS, HEPATOCYTE, GENE EXPRESSION, PHARMACOTHERAPY, TRANSCRIPTION FACTOR NETWORK, NONALCOHOLIC STEATOHEPATITIS, CONTROLLED-TRIAL, FIBROSIS, ALPHA, ACTIVATION, DISTINCT, AGONIST, RECRUITMENT, EXPRESSION

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Citation

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MLA
Dubois, Vanessa, et al. “Nuclear Receptors : Pathophysiological Mechanisms and Drug Targets in Liver Disease.” GUT, vol. 73, no. 9, 2024, pp. 1562–69, doi:10.1136/gutjnl-2023-331741.
APA
Dubois, V., Lefebvre, P., Staels, B., & Eeckhoute, J. (2024). Nuclear receptors : pathophysiological mechanisms and drug targets in liver disease. GUT, 73(9), 1562–1569. https://doi.org/10.1136/gutjnl-2023-331741
Chicago author-date
Dubois, Vanessa, Philippe Lefebvre, Bart Staels, and Jerome Eeckhoute. 2024. “Nuclear Receptors : Pathophysiological Mechanisms and Drug Targets in Liver Disease.” GUT 73 (9): 1562–69. https://doi.org/10.1136/gutjnl-2023-331741.
Chicago author-date (all authors)
Dubois, Vanessa, Philippe Lefebvre, Bart Staels, and Jerome Eeckhoute. 2024. “Nuclear Receptors : Pathophysiological Mechanisms and Drug Targets in Liver Disease.” GUT 73 (9): 1562–1569. doi:10.1136/gutjnl-2023-331741.
Vancouver
1.
Dubois V, Lefebvre P, Staels B, Eeckhoute J. Nuclear receptors : pathophysiological mechanisms and drug targets in liver disease. GUT. 2024;73(9):1562–9.
IEEE
[1]
V. Dubois, P. Lefebvre, B. Staels, and J. Eeckhoute, “Nuclear receptors : pathophysiological mechanisms and drug targets in liver disease,” GUT, vol. 73, no. 9, pp. 1562–1569, 2024.
@article{01J7N3DBM5Z0JHVR7DVVANNG3A,
  abstract     = {{Nuclear receptors (NRs) are ligand-dependent transcription factors required for liver development and function. As a consequence, NRs have emerged as attractive drug targets in a wide range of liver diseases. However, liver dysfunction and failure are linked to loss of hepatocyte identity characterised by deficient NR expression and activities. This might at least partly explain why several pharmacological NR modulators have proven insufficiently efficient to improve liver functionality in advanced stages of diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). In this perspective, we review the most recent advances in the hepatic NR field and discuss the contribution of multiomic approaches to our understanding of their role in the molecular organisation of an intricated transcriptional regulatory network, as well as in liver intercellular dialogues and interorgan cross-talks. We discuss the potential benefit of novel therapeutic approaches simultaneously targeting multiple NRs, which would not only reactivate the hepatic NR network and restore hepatocyte identity but also impact intercellular and interorgan interplays whose importance to control liver functions is further defined. Finally, we highlight the need of considering individual parameters such as sex and disease stage in the development of NR-based clinical strategies.}},
  author       = {{Dubois, Vanessa and  Lefebvre, Philippe and  Staels, Bart and  Eeckhoute, Jerome}},
  issn         = {{0017-5749}},
  journal      = {{GUT}},
  keywords     = {{LIVER FAILURE,NONALCOHOLIC STEATOHEPATITIS,HEPATOCYTE,GENE EXPRESSION,PHARMACOTHERAPY,TRANSCRIPTION FACTOR NETWORK,NONALCOHOLIC STEATOHEPATITIS,CONTROLLED-TRIAL,FIBROSIS,ALPHA,ACTIVATION,DISTINCT,AGONIST,RECRUITMENT,EXPRESSION}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1562--1569}},
  title        = {{Nuclear receptors : pathophysiological mechanisms and drug targets in liver disease}},
  url          = {{http://doi.org/10.1136/gutjnl-2023-331741}},
  volume       = {{73}},
  year         = {{2024}},
}

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