Platelet-activating factor induces matrix metalloproteinase-9 expression through Ca(2+)- or PI3K-dependent signaling pathway in a human vascular endothelial cell line

FEBS Lett. 2005 Nov 21;579(28):6451-8. doi: 10.1016/j.febslet.2005.10.027. Epub 2005 Nov 2.

Abstract

Platelet-activating factor (PAF) augments angiogenesis by promoting the synthesis of a variety of angiogenic factors, via the nuclear factor (NF)-kappaB activation. Recently, we reported that PAF upregulates MMP-9 expression in a NF-kappaB-dependent manner. In this study, we investigated the signaling pathway involved in PAF-induced MMP-9 expression in ECV304 cells. Our current data indicate that the Ca(2+)- or phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway is necessary for PAF-induced MMP-9 expression. Furthermore, PAF-induced NF-kappaB activation was blocked by selective inhibitors of Ca(2+), PI3K, or extracellular signal-regulated kinase (ERK). Our results suggest that PAF-induced MMP-9 expression, in a NF-kappaB-dependent manner, is regulated by Ca(2+), PI3K and ERK signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium / metabolism*
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / enzymology
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / metabolism*
  • Humans
  • Matrix Metalloproteinase 9 / metabolism*
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositols / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Platelet Activating Factor / pharmacology*
  • Signal Transduction
  • Up-Regulation

Substances

  • NF-kappa B
  • Phosphatidylinositols
  • Phosphoinositide-3 Kinase Inhibitors
  • Platelet Activating Factor
  • Matrix Metalloproteinase 9
  • Calcium