The inflammatory mediator oncostatin M induces angiopoietin 2 expression in endothelial cells in vitro and in vivo

J Thromb Haemost. 2010 Mar;8(3):596-604. doi: 10.1111/j.1538-7836.2010.03741.x. Epub 2009 Dec 17.

Abstract

Objectives: Members of the glycoprotein 130 (gp130) receptor-gp130 ligand family play a role in angiogenesis in different tissues. We tested the effect of this cytokine family on the angiopoietin (Ang)-Tie system, which is involved in blood vessel maturation, stabilization, and regression.

Results: Oncostatin M (OSM) increased Ang2 expression in human umbilical vein endothelial cells via Janus kinase/signal transducer and activator of transcription (JAK/STAT) and mitogen-activated protein (MAP) kinase activation. Furthermore, OSM induced Ang2 expression in macrovascular endothelial cells isolated from the human aorta and in microvascular endothelial cells isolated from human heart. Our in vivo experiments revealed that mRNA expression of Ang2 in hearts of mice injected with OSM increased significantly, and levels of OSM mRNA significantly correlated with mRNA levels of Ang2 in human hearts. In addition, OSM increased the expression of its own receptors, gp130 and OSM receptor, in endothelial cells in vitro and in mice in vivo, and levels of OSM mRNA significantly correlated with mRNA levels of gp130 and OSM receptor in human hearts.

Conclusion: Our data, showing the effects of OSM on the Ang-Tie system in endothelial cells, in hearts of mice, and in human heart tissue, provide yet another link between inflammation and angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiopoietin-2 / genetics
  • Angiopoietin-2 / metabolism*
  • Animals
  • Cells, Cultured
  • Coronary Vessels / immunology
  • Coronary Vessels / metabolism
  • Cytokine Receptor gp130 / metabolism
  • Endothelial Cells / immunology
  • Endothelial Cells / metabolism*
  • Humans
  • Inflammation Mediators / administration & dosage
  • Inflammation Mediators / metabolism*
  • Injections, Intraperitoneal
  • Janus Kinases / metabolism
  • Ligands
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • Oncostatin M / administration & dosage
  • Oncostatin M / metabolism*
  • Oncostatin M Receptor beta Subunit / metabolism
  • RNA, Messenger / metabolism
  • Recombinant Proteins / metabolism
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Time Factors
  • Tissue Culture Techniques
  • Umbilical Veins / immunology
  • Umbilical Veins / metabolism
  • Up-Regulation

Substances

  • Angiopoietin-2
  • Inflammation Mediators
  • Ligands
  • OSMR protein, human
  • Oncostatin M Receptor beta Subunit
  • Osmr protein, mouse
  • RNA, Messenger
  • Recombinant Proteins
  • STAT Transcription Factors
  • Oncostatin M
  • Cytokine Receptor gp130
  • Janus Kinases
  • Mitogen-Activated Protein Kinases