Nuclear receptors: pathophysiological mechanisms and drug targets in liver disease

Dubois, Vanessa; Lefebvre, Philippe; Staels, Bart; Eeckhoute, Jerome

Document type :

Compte-rendu et recension critique d'ouvrage

DOI :

10.1136/gutjnl-2023-331741

PMID :

38862216

Permalink :

http://hdl.handle.net/20.500.12210/118649

Title :

Nuclear receptors: pathophysiological mechanisms and drug targets in liver disease

Author(s) :

Dubois, Vanessa [Auteur]
Lefebvre, Philippe [Auteur]
Staels, Bart [Auteur]

Eeckhoute, Jerome [Auteur]

Institut National de la Santé et de la Recherche Médicale [INSERM]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Institut Pasteur de Lille
Université de Lille
Récepteurs Nucléaires, Maladies Métaboliques et Cardiovasculaires - U 1011 [RNMCD]

Journal title :

Gut

Pages :

1562-1569

Publisher :

BMJ Publishing Group

Publication date :

2024-09-11

ISSN :

0017-5749

English keyword(s) :

GENE EXPRESSION
HEPATOCYTE
LIVER FAILURE
NONALCOHOLIC STEATOHEPATITIS
PHARMACOTHERAPY

HAL domain(s) :

Sciences du Vivant [q-bio]/Médecine humaine et pathologie

English abstract : [en]

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 ...
Show more >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.Show less >

Language :

Anglais

Popular science :

Non

ANR Project :

Identification et caractérisation d'un nouveau facteur de transcription controlant l'activation des cellules stellaires et la fibrose hépatique
EGID Diabetes Pole

Collections :