Platelet-activating factor induces matrix metalloproteinase-9 expression through Ca(2+)- 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)-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.
Ko
Hyun-Mi
HM
Department of Biological Sciences, The Institute of Basic Sciences, Chonnam National University, Kwangju 500-757, Republic of Korea.
Kang
Jee-Hae
JH
Choi
Jung-Hwa
JH
Park
Sung Jun
SJ
Bai
Suk
S
Im
Suhn-Young
SY
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010972:Platelet Activating Factor / Q000494:pharmacology*; D015398:Signal Transduction; D015854:Up-Regulation
D002118:Calcium; D020780:Matrix Metalloproteinase 9; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D010716:Phosphatidylinositols; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010972:Platelet Activating Factor