Platelet-activating factor induces matrix metalloproteinase-9 expression through Ca2+- or PI3K-dependent signaling pathway in a human vascular endothelial cell line

Platelet-activating factor (PAF) augments angiogenesis by promoting the synthesis of a variety of angiogenic factors, via the nuclear factor (NF)-kappa B activation. Recently, we reported that PAF upregulates MMP-9 expression in a NF-kappa B-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 Ca2+- or phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathway is necessary for PAF-induced MMP-9 expression. Furthermore, PAF-induced NF-kappa B activation was blocked by selective inhibitors of Ca2+, PI3K, or extracellular signal-regulated kinase (ERK). Our results suggest that PAF-induced MMP-9 expression, in a NF-kappa B-dependent manner, is regulated by Ca2+, PI3K and ERK signaling pathways. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.