Platelet-derived growth factor induces tissue factor expression in vascular smooth muscle cells via activation of Egr-1
| Autor: | Christiane Viedt, Tadao Akizawa, Florian Bea, Hugo A. Katus, Jörg Kreuzer, Motohiro Kamimura |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
MAPK/ERK pathway
medicine.medical_specialty Platelet-derived growth factor Arteriosclerosis p38 mitogen-activated protein kinases medicine.medical_treatment Myocytes Smooth Muscle Becaplermin Biology p38 Mitogen-Activated Protein Kinases Muscle Smooth Vascular Immediate-Early Proteins Thromboplastin Rats Sprague-Dawley chemistry.chemical_compound Tissue factor Phosphatidylinositol 3-Kinases Internal medicine Internal Medicine medicine Animals Humans Extracellular Signal-Regulated MAP Kinases Cells Cultured Early Growth Response Protein 1 Platelet-Derived Growth Factor Kinase Growth factor Thrombosis Proto-Oncogene Proteins c-sis Cell biology Rats DNA-Binding Proteins Endocrinology src-Family Kinases chemistry Gene Expression Regulation biology.protein Signal transduction Platelet-derived growth factor receptor Signal Transduction Transcription Factors |
| Zdroj: | Hypertension (Dallas, Tex. : 1979). 44(6) |
| ISSN: | 1524-4563 |
| Popis: | Activation of vascular smooth muscle cells (SMCs) by platelet-derived growth factor (PDGF) is a seminal event in the initiation and progression of the atherosclerotic lesion and may contribute to atherosclerotic plaque instability with plaque rupture and thrombus formation. Tissue factor (TF), a prothrombotic molecule expressed by various cell types within atherosclerotic plaques, is thought to play a major role in thrombus formation after plaque rupture. This study examined intracellular signaling pathways leading to TF expression and Egr-1 activation, a key element in tissue factor transcription, by PDGF-BB in rat SMCs. PDGF-BB induced TF mRNA and protein expression in a time-dependent manner. Early growth response factor-1 (Egr-1) binding activity was also induced by PDGF-BB, as well as phosphorylation of extracellular signal-regulated kinase. PDGF-BB-induced Egr-1 activation was suppressed by inhibitors of 2 upstream activators of Egr-1, extracellular signal-regulated kinase (ERK) and Src family kinases, whereas antioxidants, phosphatidylinositol 3-phosphate kinase, and p38 MAPK inhibitors had no effect. PDGF-BB–stimulated expression of the transcriptional co-repressor NAB2 was time-dependent. Furthermore, transient transfections of SMCs with wild-type and mutated TF promoter constructs showed that the Egr-1 binding region is an important transcriptional regulator of PDGF-BB–induced TF expression. Taken together, the results suggest that PDGF-BB induces TF expression and activity in SMC by a Src family kinases/ERK/Egr-1 signaling pathway and may therefore contribute to thrombus formation in advanced atherosclerosis and restenosis. |
| Databáze: | OpenAIRE |
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