title: Involvement of matrix metalloproteinase-9 in platelet-activating factor-induced angiogenesis.
abstract: Platelet-activating factor (PAF) augments angiogenesis by promoting the synthesis of various angiogenic factors, via the activation of NF-kappaB. 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-kappaB-dependent manner. PAF increased MMP-9 promoter activity in ECV304, which was inhibited by WEB2107, and NF-kappaB inhibitors. Transfected NF-kappaB 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-kappaB 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-kappaB inhibitors inhibited PAF-induced sprouting of porcine pulmonary arterial endothelial cells. These data indicate that NF-kappaB-dependent MMP-9 plays a key role in PAF-induced angiogenesis.
authors.affiliation: Department of Biological Sciences, The Institute of Basic Sciences, Chonnam National University, Kwangju, Republic of Korea.
authors.forename: Hyun-Mi
authors.initials: HM
authors.lastname: Ko
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Bongnam
authors.initials: B
authors.lastname: Jung
authors.forename: Han-A
authors.initials: HA
authors.lastname: Kim
authors.forename: Jung-Hwa
authors.initials: JH
authors.lastname: Choi
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Park
authors.forename: Hern-Ku
authors.initials: HK
authors.lastname: Lee
authors.forename: Suhn-Young
authors.initials: SY
authors.lastname: Im
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D020780:Matrix Metalloproteinase 9