Linked Life Data

12051699

Source:http://linkedlifedata.com/resource/pubmed/id/12051699

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pubmed-article:12051699pubmed:abstractTextPlatelet-derived growth factor (PDGF) stimulates expression of matrix metalloproteinases (MMPs), including stromelysin-1 (MMP-3). Induction of these expressions is known to occur during the course of atherosclerosis, tumor invasion, and metastasis. We investigated PDGF-alpha receptor (alphaR)- and beta receptor (betaR)-mediated signaling pathways for the expression of MMP-3 and invasion activity using porcine aortic endothelial (PAE) cells with stable expression of normal or mutated PDGF receptors. RT-PCR and Western blot analyses revealed that PDGF-BB induces MMP-3 expression in PAE cells that exclusively express either the PDGF-alphaR or the -betaR, but not in non-transfected control cells. To identify the signals necessary for PDGF receptor-mediated induction of MMP-3 expression, several lines of PAE cells expressing mutant PDGF receptors were further analyzed. Cells expressing mutant PDGF receptors unable to associate with Src or PLCgamma, retained the ability to induce MMP-3 expression as a result of PDGF-BB stimulation. However, incubation with PDGF-BB did not induce MMP-3 expression in cells expressing a mutant PDGF-betaR unable to associate with phosphatidylinositol 3(')-kinase (PI3K). LY294002, a PI3K inhibitor, reduced PDGF-BB-stimulated MMP-3 expression in PAE cells expressing wild-type PDGF receptors. In contrast, PDGF-BB induced MMP-3 expression in the presence of U-73122, a PLCgamma inhibitor. Moreover, PDGF-BB enhanced the invasiveness of cells expressing wild type PDGF-beta receptors, but not of cells expressing mutant PDGF-betaRs impaired in their ability to associate with PI3K. In light of these results, it appears that PDGF-BB is capable of inducing MMP-3 expression through both the PDGF-alphaR and the -betaR, and the effects are contributed by the PI3K-mediated transduction pathways.lld:pubmed
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pubmed-article:12051699pubmed:authorpubmed-author:SaitoYasushiYlld:pubmed
pubmed-article:12051699pubmed:authorpubmed-author:TakahashiKazu...lld:pubmed
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pubmed-article:12051699pubmed:authorpubmed-author:ZhuYanjuanYlld:pubmed
pubmed-article:12051699pubmed:authorpubmed-author:KanakiTatsuro...lld:pubmed
pubmed-article:12051699pubmed:authorpubmed-author:MorisakiNobuh...lld:pubmed
pubmed-article:12051699pubmed:copyrightInfo(c) 2002 Elsevier Science (USA).lld:pubmed
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pubmed-article:12051699pubmed:dateRevised2010-11-18lld:pubmed
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pubmed-article:12051699pubmed:year2002lld:pubmed
pubmed-article:12051699pubmed:articleTitleFunctional analysis of aortic endothelial cells expressing mutant PDGF receptors with respect to expression of matrix metalloproteinase-3.lld:pubmed
pubmed-article:12051699pubmed:affiliationDepartment of Clinical Cell Biology (F5), Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.lld:pubmed
pubmed-article:12051699pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:12051699pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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