[en] The interleukin-6-type cytokine oncostatin M (OSM) acts via the Janus kinase/signal transducer and activator of transcription pathway as well as via activation of mitogen-activated protein kinases and is known to critically regulate processes such as liver development and regeneration, hematopoiesis, and angiogenesis, which are also determined by hypoxia with the hypoxia-inducible factor 1alpha (HIF1alpha) as a key component. Here we show that treatment of hepatocytes and hepatoma cells with OSM leads to an increased protein level of HIF1alpha under normoxic and hypoxic conditions. Furthermore, the OSM-dependent HIF1alpha increase is mediated via Janus kinase/signal transducer and activator of transcription 3 and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 pathways. OSM-mediated HIF1alpha up-regulation did not result from an increase in HIF1alpha protein stability but from increased transcription from the HIF1alpha gene. In addition, we show that the OSM-induced HIF1alpha gene transcription and the resulting enhanced HIF1alpha protein levels are important for the OSM-dependent vascular endothelial growth factor and plasminogen activator inhibitor 1 gene induction associated with several diseases. Conclusion: HIF1alpha levels increase significantly after treatment of hepatocytes and hepatoma cells with OSM, and HIF1alpha contributes to OSM downstream signaling events, pointing to a cross-talk between cytokine and hypoxia signaling in processes such as liver development and regeneration. (HEPATOLOGY 2009.).
Disciplines :
Biochemistry, biophysics & molecular biology
Identifiers :
UNILU:UL-ARTICLE-2009-535
Author, co-author :
VOLLMER, Stefan ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Kappler, Valérie; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
KACZOR, Jakub; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Flügel, Daniela; Chemistry Department, University of Kaiserslautern, Kaiserslautern, Germany
ROLVERING, Catherine ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Kato, Nobuyuki; Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan
Kietzmann, Thomas; Chemistry Department, University of Kaiserslautern, Kaiserslautern, Germany
BEHRMANN, Iris ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
HAAN, Claude ; University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
External co-authors :
yes
Language :
English
Title :
Hypoxia-inducible factor 1alpha is up-regulated by oncostatin M and participates in oncostatin M signaling