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Involvement of matrix metalloproteinase‐9 in platelet‐activating factor‐induced angiogenesis
Author(s) -
Ko Hyun-Mi,
Park Yeong-Min,
Jung Bongnam,
Kim Han-A,
Choi Jung-Hwa,
Park Sung Jun,
Lee Hern-Ku,
Im Suhn-Young
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.03.035
Subject(s) - angiogenesis , matrigel , luciferase , matrix metalloproteinase , chemistry , neovascularization , transfection , platelet activating factor , microbiology and biotechnology , cancer research , biology , biochemistry , immunology , gene
Platelet‐activating factor (PAF) augments angiogenesis by promoting the synthesis of various angiogenic factors, via the activation of NF‐κB. In this study, we investigated the role of the matrix metalloproteinase (MMP)‐9, in PAF‐induced angiogenesis. PAF increased mRNA expression, protein synthesis, and MMP‐9 activity in ECV304 cells, in a NF‐κB‐dependent manner. PAF increased MMP‐9 promoter activity in ECV304, which was inhibited by WEB2107, and NF‐κB inhibitors. Transfected NF‐κB subunits, p65 or/and p50, increased luciferase activity in the reporter plasmid MMP‐9, resulting in an increase not only of MMP‐9 luciferase activity, but also of mRNA expression in MMP‐9. MMP‐9 or NF‐κB inhibitors significantly inhibited PAF‐induced angiogenesis, in a dose‐dependent manner, in an in vivo mouse Matrigel implantation model. In a parallel to the Matrigel implantation study, MMP‐9 or NF‐κB inhibitors inhibited PAF‐induced sprouting of porcine pulmonary arterial endothelial cells. These data indicate that NF‐κB‐dependent MMP‐9 plays a key role in PAF‐induced angiogenesis.