Abstract
OBJECTIVE The angiopoietin-Tie2 system is an important regulator of vasculogenesis and angiogenesis. Angiopoietin2 (Ang2) acts as an antagonist of angiopoietin 1. Together with vascular endothelial growth factor (VEGF) it plays an important role in endothelial cell migration and proliferation. Previously it has been shown that Ang2 expression is upregulated by hypoxia, VEGF and basic fibroblast growth factor. There is evidence that Ang2 is also involved in inflammatory angiogenesis. We asked if there might be a link between the glycoprotein (gp) 130 ligand system, which has been shown to regulate cell proliferation and inflammatory events in other tissues, and Ang2. RESULTS OncostatinM (OSM) is the only gp130 ligand that increased Ang2 secretion in human umbilical vein endothelial cells (HUVEC) dose-dependently. These data could also be confirmed at mRNA levels. We could detect all five gp130 ligand- receptors in HUVEC and found a significant upregulation of the OSM receptor, leukemia inhibitory factor receptor and gp130 receptor by its own ligand OSM. CONCLUSION We showed for the first time a link between the gp130 ligand system and angiogenesis in HUVECs. OSM upregulates Ang2 expression and also the expression of its own receptors. This could lead to an amplification of the effect of OSM. If also operative in vivo this mechanisms would underline the role for Ang2 in inflammatory angiogenesis.
Published Version
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