Source:http://linkedlifedata.com/resource/pubmed/id/12051699
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2002-6-7
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pubmed:abstractText |
Platelet-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.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Platelet-Derived Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor BB
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0006-291X
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pubmed:author | |
pubmed:copyrightInfo |
(c) 2002 Elsevier Science (USA).
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
294
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
231-7
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12051699-Animals,
pubmed-meshheading:12051699-Aorta,
pubmed-meshheading:12051699-Cell Division,
pubmed-meshheading:12051699-Cells, Cultured,
pubmed-meshheading:12051699-Endothelium, Vascular,
pubmed-meshheading:12051699-Enzyme Inhibitors,
pubmed-meshheading:12051699-Gene Expression,
pubmed-meshheading:12051699-Humans,
pubmed-meshheading:12051699-Isoenzymes,
pubmed-meshheading:12051699-Matrix Metalloproteinase 3,
pubmed-meshheading:12051699-Mutation,
pubmed-meshheading:12051699-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:12051699-Phospholipase C gamma,
pubmed-meshheading:12051699-Platelet-Derived Growth Factor,
pubmed-meshheading:12051699-RNA, Messenger,
pubmed-meshheading:12051699-Receptor, Platelet-Derived Growth Factor alpha,
pubmed-meshheading:12051699-Receptor, Platelet-Derived Growth Factor beta,
pubmed-meshheading:12051699-Receptors, Platelet-Derived Growth Factor,
pubmed-meshheading:12051699-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12051699-Signal Transduction,
pubmed-meshheading:12051699-Swine,
pubmed-meshheading:12051699-Type C Phospholipases
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pubmed:year |
2002
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pubmed:articleTitle |
Functional analysis of aortic endothelial cells expressing mutant PDGF receptors with respect to expression of matrix metalloproteinase-3.
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pubmed:affiliation |
Department of Clinical Cell Biology (F5), Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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