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

Abstract
Platelet‐activating factor (PAF) augments angiogenesis by promoting the synthesis of a variety of angiogenic factors, via the nuclear factor (NF)‐κB activation. Recently, we reported that PAF upregulates MMP‐9 expression in a NF‐κB‐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‐κB 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‐κB‐dependent manner, is regulated by Ca2+, PI3K and ERK signaling pathways.

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