Nature Communications (Jul 2019)
Defective HNF4alpha-dependent gene expression as a driver of hepatocellular failure in alcoholic hepatitis
- Josepmaria Argemi,
- Maria U. Latasa,
- Stephen R. Atkinson,
- Ilya O. Blokhin,
- Veronica Massey,
- Joel P. Gue,
- Joaquin Cabezas,
- Juan J. Lozano,
- Derek Van Booven,
- Aaron Bell,
- Sheng Cao,
- Lawrence A. Vernetti,
- Juan P. Arab,
- Meritxell Ventura-Cots,
- Lia R. Edmunds,
- Constantino Fondevila,
- Peter Stärkel,
- Laurent Dubuquoy,
- Alexandre Louvet,
- Gemma Odena,
- Juan L. Gomez,
- Tomas Aragon,
- Jose Altamirano,
- Juan Caballeria,
- Michael J. Jurczak,
- D. Lansing Taylor,
- Carmen Berasain,
- Claes Wahlestedt,
- Satdarshan P. Monga,
- Marsha Y. Morgan,
- Pau Sancho-Bru,
- Philippe Mathurin,
- Shinji Furuya,
- Carolin Lackner,
- Ivan Rusyn,
- Vijay H. Shah,
- Mark R. Thursz,
- Jelena Mann,
- Matias A. Avila,
- Ramon Bataller
Affiliations
- Josepmaria Argemi
- Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center (UPMC)
- Maria U. Latasa
- Hepatology Program, Center for Applied Medical Research (CIMA), University of Navarra
- Stephen R. Atkinson
- Division of Digestive Diseases, Department of Surgery and Cancer, Imperial College London
- Ilya O. Blokhin
- Center for Therapeutic Innovation and Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine
- Veronica Massey
- Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill
- Joel P. Gue
- Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center (UPMC)
- Joaquin Cabezas
- Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill
- Juan J. Lozano
- Centro de Investigacion Biomedica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd)
- Derek Van Booven
- John P. Hussman Institute of Human Genomics. Miller School of Medicine, University of Miami
- Aaron Bell
- Departments of Pathology and Medicine, Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine
- Sheng Cao
- Division of Gastroenterology and Hepatology, Mayo Clinic
- Lawrence A. Vernetti
- University of Pittsburgh Drug Discovery Institute, Department of Computational & Systems Biology, University of Pittsburgh
- Juan P. Arab
- Division of Gastroenterology and Hepatology, Mayo Clinic
- Meritxell Ventura-Cots
- Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center (UPMC)
- Lia R. Edmunds
- Department of Medicine, Division of Endocrinology and Metabolism, Center for Metabolic and Mitochondrial Medicine, University of Pittsburgh
- Constantino Fondevila
- Liver Transplant Unit, Department of Surgery, Hospital Clinic, University of Barcelona
- Peter Stärkel
- Service d’Hépato-gastroentérologie, Cliniques Universitaires Saint-Luc and Laboratory of Hepatogastroenterology, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain
- Laurent Dubuquoy
- Service des Maladies de l’appareil digestif, CHU Lille. Inserm LIRIC - UMR995, University of Lille
- Alexandre Louvet
- Service des Maladies de l’appareil digestif, CHU Lille. Inserm LIRIC - UMR995, University of Lille
- Gemma Odena
- Division of Gastroenterology and Hepatology, Departments of Medicine and Nutrition and Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill
- Juan L. Gomez
- Departments of Pathology and Medicine, Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine
- Tomas Aragon
- Department of Gene Therapy and Regulation, Center for Applied Medical Research, University of Navarra
- Jose Altamirano
- Liver Unit, Department of Internal Medicine, Vall d’Hebron Institut de Recerca. Internal Medicine Department, Hospital Quiron Salud
- Juan Caballeria
- Centro de Investigacion Biomedica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd)
- Michael J. Jurczak
- Department of Medicine, Division of Endocrinology and Metabolism, Center for Metabolic and Mitochondrial Medicine, University of Pittsburgh
- D. Lansing Taylor
- University of Pittsburgh Drug Discovery Institute, Department of Computational & Systems Biology, University of Pittsburgh
- Carmen Berasain
- Hepatology Program, Center for Applied Medical Research (CIMA), University of Navarra
- Claes Wahlestedt
- Center for Therapeutic Innovation and Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine
- Satdarshan P. Monga
- Departments of Pathology and Medicine, Pittsburgh Liver Research Center, University of Pittsburgh School of Medicine
- Marsha Y. Morgan
- UCL Institute for Liver and Digestive Health, Division of Medicine, Royal Free Campus, University College London
- Pau Sancho-Bru
- Centro de Investigacion Biomedica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd)
- Philippe Mathurin
- Service des Maladies de l’appareil digestif, CHU Lille. Inserm LIRIC - UMR995, University of Lille
- Shinji Furuya
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University
- Carolin Lackner
- Medical University of Graz, Institute of Pathology
- Ivan Rusyn
- Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University
- Vijay H. Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic
- Mark R. Thursz
- Division of Digestive Diseases, Department of Surgery and Cancer, Imperial College London
- Jelena Mann
- Newcastle Fibrosis Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University
- Matias A. Avila
- Hepatology Program, Center for Applied Medical Research (CIMA), University of Navarra
- Ramon Bataller
- Division of Gastroenterology, Hepatology and Nutrition, Pittsburgh Liver Research Center, University of Pittsburgh Medical Center (UPMC)
- DOI
- https://doi.org/10.1038/s41467-019-11004-3
- Journal volume & issue
-
Vol. 10,
no. 1
pp. 1 – 19
Abstract
Alcoholic hepatitis, a common cause of liver failure, lacks effective treatment. Here, the authors show altered hepatic HNF4a isoform expression and hypermethylation of its target genes in patients. HNF4a dysregulation is improved in vitro by TGFb or PPARg modulation suggesting potential therapeutic avenues.
