BIOMAT Database Logo BIOMAT Database Logo

Platelet-derived growth factor induces tissue factor expression in vascular smooth muscle cells via activation of Egr-1. 2004

Motohiro Kamimura, and Florian Bea, and Tadao Akizawa, and Hugo A Katus, and Jörg Kreuzer, and Christiane Viedt
Innere Medizin III, Universität Heidelberg, Im Neuenheimer Feld, Heidelberg, Germany.

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.

UI MeSH Term Description Entries
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D010982 Platelet-Derived Growth Factor Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. Platelet Derived Growth Factor,Factor, Platelet-Derived Growth,Growth Factor, Platelet-Derived
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077214 Becaplermin A recombinant human platelet-derived growth factor B-chain dimer used to promote WOUND HEALING by stimulating PHYSIOLOGIC ANGIOGENESIS. PDGF-BB,Platelet-Derived Growth Factor BB,Platelet-Derived Growth Factor BB, Recombinant,Recombinant Platelet-Derived Growth Factor BB,Regranex,rPDGF-BB,rhPDGF-BB,Platelet Derived Growth Factor BB,Platelet Derived Growth Factor BB, Recombinant,Recombinant Platelet Derived Growth Factor BB
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001161 Arteriosclerosis Thickening and loss of elasticity of the walls of ARTERIES of all sizes. There are many forms classified by the types of lesions and arteries involved, such as ATHEROSCLEROSIS with fatty lesions in the ARTERIAL INTIMA of medium and large muscular arteries. Arterioscleroses
D013925 Thromboplastin Constituent composed of protein and phospholipid that is widely distributed in many tissues. It serves as a cofactor with factor VIIa to activate factor X in the extrinsic pathway of blood coagulation. Antigens, CD142,CD142 Antigens,Coagulation Factor III,Factor III,Tissue Factor,Tissue Thromboplastin,Blood Coagulation Factor III,Coagulin,Glomerular Procoagulant Activity,Prothrombinase,Tissue Factor Procoagulant,Urothromboplastin,Activity, Glomerular Procoagulant,Factor III, Coagulation,Procoagulant Activity, Glomerular,Procoagulant, Tissue Factor,Thromboplastin, Tissue

Related Publications

Motohiro Kamimura, and Florian Bea, and Tadao Akizawa, and Hugo A Katus, and Jörg Kreuzer, and Christiane Viedt
Platelet-derived growth factor induces Rad expression through Egr-1 in vascular smooth muscle cells.
April 2011, PloS one,
Motohiro Kamimura, and Florian Bea, and Tadao Akizawa, and Hugo A Katus, and Jörg Kreuzer, and Christiane Viedt
Platelet-derived growth factor induces p21/WAF1 promoter in vascular smooth muscle cells via activation of an Sp1 site.
September 2003, FEBS letters,
Motohiro Kamimura, and Florian Bea, and Tadao Akizawa, and Hugo A Katus, and Jörg Kreuzer, and Christiane Viedt
Platelet derived growth factor regulates ABCA1 expression in vascular smooth muscle cells.
August 2006, FEBS letters,
Motohiro Kamimura, and Florian Bea, and Tadao Akizawa, and Hugo A Katus, and Jörg Kreuzer, and Christiane Viedt
Homocysteine induces connective tissue growth factor expression in vascular smooth muscle cells.
January 2008, Journal of thrombosis and haemostasis : JTH,
Motohiro Kamimura, and Florian Bea, and Tadao Akizawa, and Hugo A Katus, and Jörg Kreuzer, and Christiane Viedt
Two platelet-derived growth factor receptors in vascular smooth muscle cells.
October 1991, Japanese circulation journal,
Motohiro Kamimura, and Florian Bea, and Tadao Akizawa, and Hugo A Katus, and Jörg Kreuzer, and Christiane Viedt
Ets-1 mediates platelet-derived growth factor-BB-induced thrombomodulin expression in human vascular smooth muscle cells.
March 2009, Cardiovascular research,
Motohiro Kamimura, and Florian Bea, and Tadao Akizawa, and Hugo A Katus, and Jörg Kreuzer, and Christiane Viedt
Thrombin Stimulated Platelet-Derived Exosomes Inhibit Platelet-Derived Growth Factor Receptor-Beta Expression in Vascular Smooth Muscle Cells.
January 2016, Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology,
Motohiro Kamimura, and Florian Bea, and Tadao Akizawa, and Hugo A Katus, and Jörg Kreuzer, and Christiane Viedt
Platelet-derived growth factor induces c-fms and scavenger receptor genes in vascular smooth muscle cells.
June 1992, The Journal of biological chemistry,
Motohiro Kamimura, and Florian Bea, and Tadao Akizawa, and Hugo A Katus, and Jörg Kreuzer, and Christiane Viedt
High-mobility group box 1 protein induces tissue factor expression in vascular endothelial cells via activation of NF-kappaB and Egr-1.
August 2009, Thrombosis and haemostasis,
Motohiro Kamimura, and Florian Bea, and Tadao Akizawa, and Hugo A Katus, and Jörg Kreuzer, and Christiane Viedt
Activation of Ca(2+)-Na+ exchange by platelet-derived growth factor in vascular smooth muscle cells.
January 1991, Annals of the New York Academy of Sciences,
Copied contents to your clipboard!