Defective HNF4alpha-dependent gene expression ...
Type de document :
Article dans une revue scientifique: Article original
PMID :
URL permanente :
Titre :
Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis.
Auteur(s) :
Argemi, Josepmaria [Auteur]
University of Pittsburgh [PITT]
Latasa, Maria U [Auteur]
Universidad de Navarra [Pamplona] [UNAV]
Atkinson, Stephen R [Auteur]
Imperial College London
Blokhin, Ilya O [Auteur]
University of Miami Leonard M. Miller School of Medicine [UMMSM]
Massey, Veronica [Auteur]
University of North Carolina [Chapel Hill] [UNC]
Gue, Joel P [Auteur]
University of Pittsburgh [PITT]
Cabezas, Joaquin [Auteur]
University of North Carolina [Chapel Hill] [UNC]
Lozano, Juan J [Auteur]
Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas [CIBERehd]
Van Booven, Derek [Auteur]
University of Miami Leonard M. Miller School of Medicine [UMMSM]
Bell, Aaron [Auteur]
University of Pittsburgh School of Medicine
Cao, Sheng [Auteur]
Mayo Clinic [Rochester]
Vernetti, Lawrence A [Auteur]
University of Pittsburgh [PITT]
Arab, Juan P [Auteur]
Mayo Clinic [Rochester]
Ventura-Cots, Meritxell [Auteur]
University of Pittsburgh [PITT]
Edmunds, Lia R [Auteur]
University of Pittsburgh [PITT]
Fondevilla, Constantino [Auteur]
University of Barcelona
Stärkel, Peter [Auteur]
Université Catholique de Louvain = Catholic University of Louvain [UCL]
Dubuquoy, Laurent [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Louvet, Alexandre [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Odena, Gemma [Auteur]
University of North Carolina [Chapel Hill] [UNC]
Gomez, Juan L [Auteur]
University of Pittsburgh [PITT]
Aragon, Tomas [Auteur]
Universidad de Navarra [Pamplona] [UNAV]
Altamirano, Jose [Auteur]
Vall d'Hebron University Hospital [Barcelona]
Caballeria, Juan [Auteur]
Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas [CIBERehd]
Jurczak, Michael J [Auteur]
University of Pittsburgh [PITT]
Taylor, D Lansing [Auteur]
University of Pittsburgh [PITT]
Berasain, Carmen [Auteur]
Universidad de Navarra [Pamplona] [UNAV]
Wahlestedt, Claes [Auteur]
University of Miami Leonard M. Miller School of Medicine [UMMSM]
Monga, Satdarshan P [Auteur]
University of Pittsburgh School of Medicine
Morgan, Marsha Y [Auteur]
University College of London [London] [UCL]
Sancho-Bru, Pau [Auteur]
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Mathurin, Philippe [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Furuya, Shinji [Auteur]
Texas A&M University [College Station]
Lackner, Carolin [Auteur]
Medical University Graz
Rusyn, Ivan [Auteur]
Texas A&M University [College Station]
Shah, Vijay H [Auteur]
Mayo Clinic [Rochester]
Thursz, Mark R [Auteur]
Imperial College London
Mann, Jelena [Auteur]
Newcastle University [Newcastle]
Avila, Matias A [Auteur]
Universidad de Navarra [Pamplona] [UNAV]
Bataller, Ramon [Auteur]
University of North Carolina [Chapel Hill] [UNC]
University of Pittsburgh [PITT]
Latasa, Maria U [Auteur]
Universidad de Navarra [Pamplona] [UNAV]
Atkinson, Stephen R [Auteur]
Imperial College London
Blokhin, Ilya O [Auteur]
University of Miami Leonard M. Miller School of Medicine [UMMSM]
Massey, Veronica [Auteur]
University of North Carolina [Chapel Hill] [UNC]
Gue, Joel P [Auteur]
University of Pittsburgh [PITT]
Cabezas, Joaquin [Auteur]
University of North Carolina [Chapel Hill] [UNC]
Lozano, Juan J [Auteur]
Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas [CIBERehd]
Van Booven, Derek [Auteur]
University of Miami Leonard M. Miller School of Medicine [UMMSM]
Bell, Aaron [Auteur]
University of Pittsburgh School of Medicine
Cao, Sheng [Auteur]
Mayo Clinic [Rochester]
Vernetti, Lawrence A [Auteur]
University of Pittsburgh [PITT]
Arab, Juan P [Auteur]
Mayo Clinic [Rochester]
Ventura-Cots, Meritxell [Auteur]
University of Pittsburgh [PITT]
Edmunds, Lia R [Auteur]
University of Pittsburgh [PITT]
Fondevilla, Constantino [Auteur]
University of Barcelona
Stärkel, Peter [Auteur]
Université Catholique de Louvain = Catholic University of Louvain [UCL]
Dubuquoy, Laurent [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Louvet, Alexandre [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Odena, Gemma [Auteur]
University of North Carolina [Chapel Hill] [UNC]
Gomez, Juan L [Auteur]
University of Pittsburgh [PITT]
Aragon, Tomas [Auteur]
Universidad de Navarra [Pamplona] [UNAV]
Altamirano, Jose [Auteur]
Vall d'Hebron University Hospital [Barcelona]
Caballeria, Juan [Auteur]
Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas [CIBERehd]
Jurczak, Michael J [Auteur]
University of Pittsburgh [PITT]
Taylor, D Lansing [Auteur]
University of Pittsburgh [PITT]
Berasain, Carmen [Auteur]
Universidad de Navarra [Pamplona] [UNAV]
Wahlestedt, Claes [Auteur]
University of Miami Leonard M. Miller School of Medicine [UMMSM]
Monga, Satdarshan P [Auteur]
University of Pittsburgh School of Medicine
Morgan, Marsha Y [Auteur]
University College of London [London] [UCL]
Sancho-Bru, Pau [Auteur]
Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
Mathurin, Philippe [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Furuya, Shinji [Auteur]
Texas A&M University [College Station]
Lackner, Carolin [Auteur]
Medical University Graz
Rusyn, Ivan [Auteur]
Texas A&M University [College Station]
Shah, Vijay H [Auteur]
Mayo Clinic [Rochester]
Thursz, Mark R [Auteur]
Imperial College London
Mann, Jelena [Auteur]
Newcastle University [Newcastle]
Avila, Matias A [Auteur]
Universidad de Navarra [Pamplona] [UNAV]
Bataller, Ramon [Auteur]
University of North Carolina [Chapel Hill] [UNC]
Titre de la revue :
Nature Communications
Nom court de la revue :
Nat Commun
Numéro :
10
Pagination :
3126
Date de publication :
2019-07-16
ISSN :
2041-1723
Mot(s)-clé(s) en anglais :
Adult
Aged
Animals
Biopsy
Chromatin Assembly and Disassembly
DNA Methylation
Disease Progression
Epigenesis, Genetic
Female
Gene Expression Profiling
Gene Expression Regulation
Hepatitis, Alcoholic
Hepatocyte Nuclear Factor 4
Hepatocytes
Humans
Liver
Male
Middle Aged
Polymorphism, Genetic
Sequence Analysis, RNA
Transforming Growth Factor beta1
Aged
Animals
Biopsy
Chromatin Assembly and Disassembly
DNA Methylation
Disease Progression
Epigenesis, Genetic
Female
Gene Expression Profiling
Gene Expression Regulation
Hepatitis, Alcoholic
Hepatocyte Nuclear Factor 4
Hepatocytes
Humans
Liver
Male
Middle Aged
Polymorphism, Genetic
Sequence Analysis, RNA
Transforming Growth Factor beta1
Discipline(s) HAL :
Sciences du Vivant [q-bio]
Résumé en anglais : [en]
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 ...
Lire la suite >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.Lire moins >
Lire la suite >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.Lire moins >
Comité de lecture :
Oui
Audience :
Non spécifiée
Établissement(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Date de dépôt :
2021-01-14T08:55:42Z
2021-01-18T08:58:07Z
2021-01-18T08:58:07Z
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