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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2010-3-3
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pubmed:abstractText |
Tissue factor (TF) is the principal trigger of the coagulation cascade and involved in arterial thrombus formation. Platelet-derived growth factor CC (PDGF-CC) is a recently discovered member of the PDGF family released upon platelet activation. This study assesses the impact of PDGF-CC on TF expression in human cells. PDGF-CC concentration-dependently induced TF expression by 2.5-fold in THP-1 cells, by 2.0-fold in human peripheral blood monocytes, by 1.4-fold in vascular smooth muscle cells, and by 2.6-fold in microvascular endothelial cells, but did not affect TF expression in aortic endothelial cells. A similar pattern was observed with PDGF-BB. In contrast, PDGF-AA did not alter TF expression in THP-1 cells. TF whole cell activity was induced following stimulation with PDGF-BB and PDGF-CC in THP-1 cells. Real-time polymerase chain reaction revealed that PDGF-CC induced TF mRNA. PDGF-CC transiently activated p42/44 MAP kinase [extracellular signal-regulated kinase (ERK)], while phosphorylation of the MAP kinases c-Jun NH(2)-terminal kinase (JNK) and p38 remained unaffected. PD98059, a specific inhibitor of ERK phosphorylation, but not the p38 inhibitor SB203580 or the JNK inhibitor SP600125 prevented PDGF-CC induced TF expression in a concentration-dependent manner. The effect of PDGF-CC was antagonized by both PDGF receptor alpha and PDGF receptor beta neutralizing antibodies; in contrast, PDGF-BB was only inhibited by PDGF receptor beta blocking antibody. PDGF receptor alpha and PDGF receptor beta inhibition prevented PDGF-CC-induced ERK phosphorylation. PDGF-CC induces TF expression via activation of alpha/beta receptor heterodimers and an ERK-dependent signal transduction pathway.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Flavonoids,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/PD 98059,
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/Thromboplastin,
http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor BB,
http://linkedlifedata.com/resource/pubmed/chemical/platelet-derived growth factor C
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1435-1803
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
105
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
349-56
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pubmed:meshHeading |
pubmed-meshheading:19795151-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:19795151-Cells, Cultured,
pubmed-meshheading:19795151-Dose-Response Relationship, Drug,
pubmed-meshheading:19795151-Endothelium, Vascular,
pubmed-meshheading:19795151-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:19795151-Flavonoids,
pubmed-meshheading:19795151-Humans,
pubmed-meshheading:19795151-Leukocytes, Mononuclear,
pubmed-meshheading:19795151-Lymphokines,
pubmed-meshheading:19795151-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:19795151-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:19795151-Muscle, Smooth, Vascular,
pubmed-meshheading:19795151-Platelet-Derived Growth Factor,
pubmed-meshheading:19795151-RNA, Messenger,
pubmed-meshheading:19795151-Receptor, Platelet-Derived Growth Factor alpha,
pubmed-meshheading:19795151-Receptor, Platelet-Derived Growth Factor beta,
pubmed-meshheading:19795151-Thromboplastin
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pubmed:year |
2010
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pubmed:articleTitle |
PDGF-CC induces tissue factor expression: role of PDGF receptor alpha/beta.
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pubmed:affiliation |
Cardiovascular Research, Physiology Institute, University of Zurich, Zurich, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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