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dc.creatorArgemí, J. (Josepmaria)-
dc.creatorLatasa, M.U. (María Ujué)-
dc.creatorAtkinson, S.R. (Stephen R.)-
dc.creatorBlokhin, I.O. (Ilya O.)-
dc.creatorMassey, V. (Veronica)-
dc.creatorGue, J.P. (Joel P.)-
dc.creatorCabezas, J. (Joaquín)-
dc.creatorLozano, J.J. (Juan J.)-
dc.creatorVan-Booven, D. (Derek)-
dc.creatorBell, A. (Aaron)-
dc.creatorCao, S. (Sheng)-
dc.creatorVernetti, L.A. (Lawrence A.)-
dc.creatorArab, J.P. (Juan P.)-
dc.creatorVentura-Cots, M. (Meritxell)-
dc.creatorEdmunds, L.R. (Lia R.)-
dc.creatorFondevilla, C. (Constantino)-
dc.creatorStärkel, P. (Peter)-
dc.creatorDubuquoy, L. (Laurent)-
dc.creatorLouvet, A. (Alexandre)-
dc.creatorOdena, G. (Gemma)-
dc.creatorGómez, J.L. (Juan L.)-
dc.creatorAragón, T. (Tomás)-
dc.creatorAltamirano, J. (Jose)-
dc.creatorCaballeria, J. (Juan)-
dc.creatorJurczak, M.J. (Michael J.)-
dc.creatorTaylor, D.L. (D. Lansing)-
dc.creatorBerasain, C. (Carmen)-
dc.creatorWahlestedt, C. (Claes)-
dc.creatorMonga, S.P. (Satdarshan P.)-
dc.creatorMorgan, M.Y. (Marsha Y.)-
dc.creatorSancho-Bru, P. (Pau)-
dc.creatorMathurin, P. (Philippe)-
dc.creatorFuruya, S. (Shinji)-
dc.creatorLackner, C. (Carolin)-
dc.creatorRusyn, I. (Ivan)-
dc.creatorShah, V.H. (Vijay H.)-
dc.creatorThursz, M.R. (Mark R.)-
dc.creatorMann, J. (Jelena)-
dc.creatorAvila, M.A. (Matías Antonio)-
dc.creatorBataller, R. (Ramón)-
dc.identifier.citationArgemí, J. (Josepmaria); Latasa, M.U. (María Ujué); Atkinson, S.R. (Stephen R.); et al. "Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis". Nature Communications. 10 (3126), 2019, 1 - 19es
dc.identifier.otherPMID: 31311938-
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.es_ES
dc.description.sponsorshipThis 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, Fundación 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 médicale (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.). Acronyms: NIH: National Institutes of Health; NIAAA: National Institute of Alcohol Abuse and Alcoholism; MRC: Medical Research Council; NCATS: National Center for Advancing Translational Sciences; EPA: United States Environmental Protection Agency; STAR: Science to Achieve Results; NIHR: National Institute for Health Research; AFEF: Association Française Pour l’Etude du Foie.es_ES
dc.publisherSpringer Science and Business Media LLCes_ES
dc.subjectMaterias Investigacion::Ciencias de la Salud::Hepatologíaes_ES
dc.titleDefective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitises_ES
dc.description.noteThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.es_ES
dadun.citation.publicationNameNature Communicationses_ES

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