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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorArgemi, Josepmaria
dc.contributor.authorLatasa, Maria U.
dc.contributor.authorAtkinson, Stephen R.
dc.contributor.authorBlokhin, Ilya O.
dc.contributor.authorMassey, Veronica
dc.contributor.authorGue, Joel P.
dc.contributor.authorAltamirano Gómez, José
dc.date.accessioned2020-02-12T12:52:44Z
dc.date.available2020-02-12T12:52:44Z
dc.date.issued2019-07-16
dc.identifier.citationArgemi 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.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11351/4617
dc.descriptionRNA sequencing in livers; TGFβ1; Epigenetic drivers
dc.description.abstractAlcoholic 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.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofseriesNature Communications;10(1)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectHepatitis
dc.subjectÀcids nucleics - Anàlisi
dc.subjectEpigenètica
dc.subject.meshHepatitis, Alcoholic
dc.subject.meshSequence Analysis, RNA
dc.subject.meshEpigenesis, Genetic
dc.titleDefective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1038/s41467-019-11004-3
dc.subject.decshepatitis alcohólica
dc.subject.decsanálisis de secuencias de ARN
dc.subject.decsepigénesis genética
dc.relation.publishversionhttps://www.nature.com/articles/s41467-019-11004-3#Sec32
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.authoraffiliation[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.identifier.pmid31311938
dc.identifier.wos000475566800007
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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