Back
Full-text
Journal article

Krüppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury.

  • Sydor S Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
  • Manka P Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
  • Best J Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
  • Jafoui S Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
  • Sowa JP Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
  • Zoubek ME Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
  • Hernandez-Gea V Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (Ciberehd), Villarroel 170, 08036, Barcelona, Spain.
  • Cubero FJ Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
  • Kälsch J Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
  • Vetter D Department of Surgery, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.
  • Fiel MI Division of Liver Diseases, Department of Medicine and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave., New York, NY, 10029, USA.
  • Hoshida Y Division of Liver Diseases, Department of Medicine and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave., New York, NY, 10029, USA.
  • Bian CB Division of Liver Diseases, Department of Medicine and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave., New York, NY, 10029, USA.
  • Nelson LJ Institute for Bio Engineering (IBioE), Human Tissue Engineering, Faraday Building, The University of Edinburgh, The King's Buildings, Mayfield Road, Edinburgh, EH9 3JL, Scotland, United Kingdom.
  • Moshage H Department of Gastroenterology and Hepatology, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
  • Faber KN Department of Gastroenterology and Hepatology, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
  • Paul A Department of General- and Transplant-Surgery, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
  • Baba HA Department of Pathology, University Hospital of Essen, Hufelandstrasse 55, 45147, Essen, Germany.
  • Gerken G Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
  • Friedman SL Division of Liver Diseases, Department of Medicine and Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave., New York, NY, 10029, USA.
  • Canbay A Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany.
  • Bechmann LP Department of Gastroenterology and Hepatology, University Hospital Essen, Hufelandstrasse 55, 45147, Essen, Germany. lars.bechmann@med.ovgu.de.
Show more…
  • 2017-08-16
Published in:
  • Scientific reports. - 2017
Acetaminophen
Acute Lung Injury
Animals
Autophagy
Carbon Tetrachloride
Carcinoma, Hepatocellular
Cell Line, Tumor
Cell Proliferation
Gene Expression Regulation
Genes, Tumor Suppressor
Hep G2 Cells
Hepatectomy
Hepatocytes
Humans
Kruppel-Like Factor 6
Liver
Liver Neoplasms
Liver Regeneration
Mice
Mice, Inbred C57BL
Transcription, Genetic
Transcriptional Activation
English Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice. In mice with hepatocyte-specific Klf6 knockout (DeltaKlf6), cell proliferation following partial hepatectomy (PHx) was increased compared to controls. Interestingly, key autophagic markers and mediators LC3-II, Atg7 and Beclin1 were reduced in DeltaKlf6 mice livers. Using luciferase assay and ChIP, KLF6 was established as a direct transcriptional activator of ATG7 and BECLIN1, but was dependent on the presence of p53. Here we show, that KLF6 expression is induced in ALF and in the regenerating liver, where it activates autophagy by transcriptional induction of ATG7 and BECLIN1 in a p53-dependent manner. These findings couple the activity of an important growth inhibitor in liver to the induction of autophagy in hepatocytes.
Language
  • English
Open access status
gold
Identifiers
Persistent URL
https://sonar.ch/global/documents/30355
Statistics
Document views: 62 File downloads:
  • Full-text: 0