Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-6-7
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0006-291X
pubmed:author
pubmed:copyrightInfo
(c) 2002 Elsevier Science (USA).
pubmed:issnType
Print
pubmed:day
7
pubmed:volume
294
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
231-7
pubmed:dateRevised
2010-11-18
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
pubmed:year
2002
pubmed:articleTitle
Functional analysis of aortic endothelial cells expressing mutant PDGF receptors with respect to expression of matrix metalloproteinase-3.
pubmed:affiliation
Department of Clinical Cell Biology (F5), Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't