FOXA2 prevents hyperbilirubinaemia in acute liver failure by maintaining apical MRP2 expression.

Animals Mice Bilirubin Hepatocyte Nuclear Factor 3-beta / metabolism Hepatocytes / metabolism Hyperbilirubinemia / metabolism Lipopolysaccharides / metabolism Liver / metabolism Liver Failure, Acute / metabolism Multidrug Resistance-Associated Protein 2 / metabolism ATP-Binding Cassette Sub-Family B Member 4
ACUTE LIVER FAILURE CHOLESTASIS SEPSIS

Journal

Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R

Informations de publication

Date de publication:
03 2023
Historique:
received: 17 01 2022
accepted: 04 04 2022
pubmed: 22 4 2022
medline: 10 2 2023
entrez: 21 4 2022
Statut: ppublish

Résumé

Multidrug resistance protein 2 (MRP2) is a bottleneck in bilirubin excretion. Its loss is sufficient to induce hyperbilirubinaemia, a prevailing characteristic of acute liver failure (ALF) that is closely associated with clinical outcome. This study scrutinises the transcriptional regulation of MRP2 under different pathophysiological conditions. Hepatic MRP2, farnesoid X receptor (FXR) and Forkhead box A2 (FOXA2) expression and clinicopathologic associations were examined by immunohistochemistry in 14 patients with cirrhosis and 22 patients with ALF. MRP2 regulatory mechanisms were investigated in primary hepatocytes, Physiologically, homeostatic MRP2 transcription is mediated by the nuclear receptor FXR/retinoid X receptor complex. FOXA2 replaces FXR to maintain MRP2 expression in ALF without sepsis. Ectopic FOXA2 expression to maintain MRP2 represents a potential strategy to prevent hyperbilirubinaemia in septic ALF.

Identifiants

DOI: 10.1136/gutjnl-2022-326987 PMID: 35444014
pubmed: 35444014
pii: gutjnl-2022-326987
doi: 10.1136/gutjnl-2022-326987
doi:

Substances chimiques

Bilirubin RFM9X3LJ49
Foxa2 protein, mouse 0
Hepatocyte Nuclear Factor 3-beta 135845-92-0
Lipopolysaccharides 0
Multidrug Resistance-Associated Protein 2 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

549-559

Commentaires et corrections

Type : CommentIn

Informations de copyright

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Sai Wang (S)

Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Rilu Feng (R)

Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Shan Shan Wang (SS)

Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Beijing Institute of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China.

Hui Liu (H)

Department of Pathology, Beijing You'an Hospital, Affiliated with Capital Medical University, Beijing, China.

Chen Shao (C)

Department of Pathology, Beijing You'an Hospital, Affiliated with Capital Medical University, Beijing, China.

Yujia Li (Y)

Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Frederik Link (F)

Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Stefan Munker (S)

Department of Medicine II, University Hospital, LMU, Munich, Germany.
Liver Center Munich, University Hospital, LMU, Munich, Germany.

Roman Liebe (R)

Clinic of Gastroenterology, Hepatology and Infectious Diseases, Heinrich Heine University, Düsseldorf, Germany.
Department of Medicine II, Saarland University Medical Centre, Saarland University, Homburg, Germany.

Christoph Meyer (C)

Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Elke Burgermeister (E)

Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
ORCID: 0000-0002-4969-5697

Matthias Ebert (M)

Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Mannheim Institute for Innate Immunoscience (MI3), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Clinical Cooperation Unit Healthy Metabolism, Center of Preventive Medicine and Digital Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Steven Dooley (S)

Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.

Huiguo Ding (H)

Department of Gastroenterology and Hepatology, Beijing You'an Hospital, Affiliated with Capital Medical University, Beijing, China.

Honglei Weng (H)

Department of Medicine II, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany honglei.weng@medma.uni-heidelberg.de.
ORCID: 0000-0002-9731-3948

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › FOXA2 prevents hyperbilirubinaemia in acute...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › FOXA2 prevents hyperbilirubinaemia in acute...
questionsmedicales.fr › Facteurs biologiques › Pigments biologiques › Pigments biliaires › Bilirubine › FOXA2 prevents hyperbilirubinaemia in acute...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif hélice ailée › Facteurs de transcription Forkhead › Facteur nucléaire hépatocytaire HNF-3 bêta › FOXA2 prevents hyperbilirubinaemia in acute...
questionsmedicales.fr › Cellules › Cellules épithéliales › Hépatocytes › FOXA2 prevents hyperbilirubinaemia in acute...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Hyperbilirubinémie › FOXA2 prevents hyperbilirubinaemia in acute...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Toxines bactériennes › Endotoxines › Lipopolysaccharides › FOXA2 prevents hyperbilirubinaemia in acute...
questionsmedicales.fr › Système digestif › Foie › FOXA2 prevents hyperbilirubinaemia in acute...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Insuffisance hépatique › Défaillance hépatique › Défaillance hépatique aigüe › FOXA2 prevents hyperbilirubinaemia in acute...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Protéines de transport membranaire › Pompes ioniques › Transporteurs d'anions › Transporteurs d'anions organiques › Transporteurs d'anions organiques ATP-dépendants › Protéines associées à la multirésistance aux médicaments › Protéine-2 associée à la multirésistance aux médicaments › FOXA2 prevents hyperbilirubinaemia in acute...