dc.contributor
[Argemi J] Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, Pittsburgh, USA. University of Pittsburgh Medical Center (UPMC), Pittsburgh, USA. Liver Unit, Clínica Universidad de Navarra, Navarra, Pamplona. University of Navarra, Pamplona, Spain. [Latasa MU] Hepatology Program, Center for Applied Medical Research (CIMA), University of Navarra, Pamplona, Spain. [Atkinson SR] Division of Digestive Diseases, Department of Surgery and Cancer, Imperial College London, London, UK. [Blokhin IO] Center for Therapeutic Innovation and Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, USA. [Massey V] Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, USA. [Gue JP] Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, Pittsburgh, USA. University of Pittsburgh Medical Center (UPMC), Pittsburgh, USA. [Altamirano J] Servei de Medicina Interna, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Departament de Medicina Interna, Hospital Quiron Salud, Barcelona, Spain.
dc.contributor
Vall d'Hebron Barcelona Hospital Campus
dc.contributor.author
Argemi, Josepmaria
dc.contributor.author
Latasa, Maria U.
dc.contributor.author
Atkinson, Stephen R.
dc.contributor.author
Blokhin, Ilya O.
dc.contributor.author
Massey, Veronica
dc.contributor.author
Gue, Joel P.
dc.contributor.author
Altamirano Gómez, José
dc.date.accessioned
2025-10-24T08:50:57Z
dc.date.available
2025-10-24T08:50:57Z
dc.date.issued
2020-02-12T12:52:44Z
dc.date.issued
2020-02-12T12:52:44Z
dc.date.issued
2019-07-16
dc.identifier
Argemi J, Latasa MU, Atkinson SR, Blokhin IO, Massey V, Gue JP, et al. Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis. Nat Commun. 2019;10(1):3126.
dc.identifier
https://hdl.handle.net/11351/4617
dc.identifier
10.1038/s41467-019-11004-3
dc.identifier
000475566800007
dc.identifier.uri
http://hdl.handle.net/11351/4617
dc.description.abstract
RNA sequencing in livers; TGFβ1; Epigenetic drivers
dc.description.abstract
Seqüenciació d’ARN en el fetge; TGFβ1; Controladors epigenètics
dc.description.abstract
Secuenciación de ARN en el hígado; TGFβ1; Controladores epigenéticos
dc.description.abstract
Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH.
dc.description.abstract
This work was mainly supported by NIH/NIAAA funded Consortia "Integrated approaches for identifying molecular targets in alcoholic hepatitis" InTEAM (U01AA021908) (R.B., P.M., P.S-B., I.R., J.Cbl). This work was supported in part by: NIH/NIAAA (R01AA023781), USA (C.W.); Hepacare Project, Fundacion La Caixa, Spain (M.A.A., C.B. and M.U.L); Fond national de la recherche scientifique (FNRS J.0146.17) and Fond de la recherche scientifique medicale (FRSM T.0217.18), Belgium (P.S.); NIH/NCATS (UH3TR000503) and EPA (STAR 83573601), USA (D.L.V. and L.A.T.); MRC, UK (MK/K001949/1) and NIH/NIAAA, USA (UO1AA018663) (J.M.); NIH/NIAAA (1U01AA021908-01-33490), Instituto de Salud Carlos III (PI17/00673) and Miguel Servet (CPII16/00041) and "Una manera de hacer Europa" program, European Regional Development Fund (ERDF), EU (P.S-B.); National Institute for Health Research Imperial Biomedical Research Centre and NIHR Health Technology Assessment Grant 08-14-44 (M.R.T.); NIH T32, DK007052, USA (L.R.E.); NIH/NIAAA (1U01AA021908) and AFEF (P.M., L.D., A. L.).
dc.format
application/pdf
dc.format
application/pdf
dc.publisher
Nature Publishing Group
dc.relation
Nature Communications;10(1)
dc.relation
https://www.nature.com/articles/s41467-019-11004-3#Sec32
dc.rights
Attribution-NonCommercial-NoDerivatives 4.0 International
dc.rights
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights
info:eu-repo/semantics/openAccess
dc.subject
Àcids nucleics - Anàlisi
dc.subject
DISEASES::Digestive System Diseases::Liver Diseases::Hepatitis::Hepatitis, Alcoholic
dc.subject
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, RNA
dc.subject
PHENOMENA AND PROCESSES::Genetic Phenomena::Gene Expression Regulation::Epigenesis, Genetic
dc.subject
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades hepáticas::hepatitis::hepatitis alcohólica
dc.subject
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::técnicas genéticas::análisis de secuencias::análisis de secuencias de ARN
dc.subject
FENÓMENOS Y PROCESOS::fenómenos genéticos::regulación de la expresión génica::epigénesis genética
dc.title
Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis
dc.type
info:eu-repo/semantics/article
dc.type
info:eu-repo/semantics/publishedVersion
