Hypoxia-inducible factor 1α is up-regulated by oncostatin M and participates in oncostatin M signaling

Stefan Vollmer, Valérie Kappler, Jakub Kaczor, Daniela Flügel, Catherine Rolvering, Nobuyuki Kato, Thomas Kietzmann, Iris Behrmann, Claude Haan

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

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 1α(HIF1α) as a key component. Here we show that treatment of hepatocytes and hepatoma cells with OSM leads to an increased protein level of HIF1α under normoxic and hypoxic conditions. Furthermore, the OSM-dependent HIF1α 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 HIF1α up-regulation did not result from an increase in HIF1α protein stability but from increased transcription from the HIF1α gene. In addition, we show that the OSM-induced HIF1α gene transcription and the resulting enhanced HIF1α protein levels are important for the OSM-dependent vascular endothelial growth factor and plasminogen activator inhibitor 1 gene induction associated with several diseases. Conclusion: HIF1α levels increase significantly after treatment of hepatocytes and hepatoma cells with OSM, and HIF1α contributes to OSM downstream signaling events, pointing to a cross-talk between cytokine and hypoxia signaling in processes such as liver development and regeneration.

Original languageEnglish
Pages (from-to)253-260
Number of pages8
JournalHepatology
Volume50
Issue number1
DOIs
Publication statusPublished - 2009

ASJC Scopus subject areas

  • Hepatology

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