Thrombin- and Factor Xa–Induced DNA Synthesis Is Mediated by Transactivation of Fibroblast Growth Factor Receptor-1 in Human Vascular Smooth Muscle Cells

Rauch, Bernhard; Millette, Esther; Kenagy, Richard D.; Daum, Guenter; Clowes, Alexander W.

doi:10.1161/01.res.0000111805.09592.d8

Cited by 75 publications

(63 citation statements)

References 31 publications

(32 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There could be three possible explanations for this phenomenon. First, Rauch and co-workers previously found that FGF2 is required for the thrombin and FXa-induced, PAR-1 mediated DNA synthesis (33). Our finding that the antagonistic effect of TFPI against retinoblastoma cell proliferation only worked under the supplement of exogenous FGF2 might be explained by this permissive role of FGF2.…”

Section: Discussionsupporting

confidence: 49%

Tissue factor is involved in retinoblastoma cell proliferation via both the Akt and extracellular signal-regulated kinase pathways

Lee

Kim²,

Woo

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

Abstract. Tissue factor (TF) is known to play a role in tumor progression. In retinoblastoma, the expression and role of TF has not been determined yet. Herein, we demonstrated for the first time that TF is closely related to the proliferation of retinoblastoma cells, which could be therefore effectively suppressed by blockade of the TF pathway. TF was selectively expressed on the areas of highly mitogenic activity in an orthotopic transplantation mouse model of retinoblastoma. In addition, the levels of TF expression in retinoblastoma cells were elevated after FGF2 treatment, whereas the proliferative effect of FGF2 on retinoblastoma cells was significantly inhibited by blockade of the TF pathway via TF pathway inhibitor (TFPI). Interestingly, retinoblastoma cells cultured with FGF2 showed increased phosphorylation of both Akt and ERK1/2. Addition of TFPI nearly abolished the FGF2-induced phosphorylation of Akt and ERK1/2 in retinoblastoma cells. Therefore, our data suggest that TF expression in retinoblastoma cells is closely related to tumor cell proliferation and TFPI has the potential to inhibit retinoblastoma cell proliferation via the inhibition of both Akt and ERK1/2 activation.

show abstract

Section: Discussionsupporting

confidence: 49%

Tissue factor is involved in retinoblastoma cell proliferation via both the Akt and extracellular signal-regulated kinase pathways

Lee

Kim²,

Woo

et al. 2011

Oncol Rep

View full text Add to dashboard Cite

show abstract

“…The receptors for epidermal growth factor, platelet-derived growth factor, insulin-like growth factor-1, FGFs and neurotrophins can thus be transactivated in response to GPCR activation in the absence of neurotrophic factor binding at the cell surface via direct (heteromeric receptor complexes) and/or indirect GPCR/RTK receptor interactions (Kang and Schuman, 1995;Luttrell et al, 1999;Lee and Chao, 2001;Lee et al, 2002a,b;Kotecha et al, 2002;Ferguson, 2003;Rauch et al, 2004;Shah and Catt, 2004;Rajagopal et al, 2004;Berghuis et al, 2005). This RTK transactivation via GPCR-RTK receptor interactions (Fig.…”

Section: Transactivation Of Receptor Tyrosine Kinases Following G-promentioning

confidence: 99%

From the Golgi–Cajal mapping to the transmitter-based characterization of the neuronal networks leading to two modes of brain communication: Wiring and volume transmission

Fuxé¹,

Dahlström²,

Höistad³

et al. 2007

Brain Research Reviews

209

219

View full text Add to dashboard Cite

After Golgi-Cajal mapped neural circuits, the discovery and mapping of the central monoamine neurons opened up for a new understanding of interneuronal communication by indicating that another form of communication exists. For instance, it was found that dopamine may be released as a prolactin inhibitory factor from the median eminence, indicating an alternative mode of dopamine communication in the brain. Subsequently, the analysis of the locus coeruleus noradrenaline neurons demonstrated a novel type of lower brainstem neuron that monosynaptically and globally innervated the entire CNS.Furthermore, the ascending raphe serotonin neuron systems were found to globally innervate the forebrain with few synapses, and where deficits in serotonergic function appeared to play a major role in depression. We propose that serotonin reuptake This will lead to the unified execution of information handling and trophism for optimal brain function and survival.

show abstract

“…14,15 Subconfluent cells at passages 4 to 9 were serum deprived for 48 hours before the experiments.…”

Section: Cell Culturementioning

confidence: 99%

Regulation of Functionally Active P2Y12 ADP Receptors by Thrombin in Human Smooth Muscle Cells and the Presence of P2Y12 in Carotid Artery Lesions

Rauch

Rosenkranz

Ermler

et al. 2010

ATVB

Self Cite

View full text Add to dashboard Cite

Objective-The platelet P2Y12 ADP receptor is a well-known target of thienopyridine-type antiplatelet drugs. This study is the first to describe increased transcriptional expression of a functionally active P2Y12 in response to thrombin in human vascular smooth muscle cells (SMC). Methods and Results-On exposure to thrombin, P2Y12 mRNA was transiently increased, whereas total protein and cell surface expression of P2Y12 were markedly increased within 6 hours and remained elevated over 24 hours. This effect was mediated by activation of nuclear factor B. Preincubation with thrombin significantly enhanced the efficacy of the P2Y receptor agonist 2-methylthio-ADP to induce interleukin 6 expression and SMC mitogenesis. Effects induced by 2-methylthio-ADP were prevented by RNA interference-mediated knockdown of P2Y12 and a selective P2Y12-antagonist R-138727, the active metabolite of prasugrel. In addition, positive P2Y12 immunostaining was shown in SMC of human carotid artery plaques and was found to colocalize with tissue factor, the rate-limiting factor of thrombin formation in vivo. Conclusion-These data suggest that the P2Y12 receptor not only is central to ADP-induced platelet activation but also may mediate platelet-independent responses, specifically under conditions of enhanced thrombin formation, such as local vessel injury and atherosclerotic plaque rupture. Key Words: atherosclerosis Ⅲ thrombin Ⅲ P2Y12 receptor Ⅲ inflammation Ⅲ vascular smooth muscle P 2Y12 ADP receptor antagonists, such as the thienopyridines, are widely used as antiplatelet drugs. 1,2 Besides their role as inhibitors of platelet aggregation, there is increasing evidence that these compounds also exert antiinflammatory actions. Reduced plasma levels of inflammatory markers, such as CD40 ligand, C-reactive protein, P-selectin, and platelet-leukocyte aggregates, have been shown with P2Y12 antagonists in atherothrombotic patients, 3 and platelet P2Y12 has also been shown recently to influence vessel wall responses to injury and thrombosis. 4 Thus far, these effects have been attributed solely to the antiplatelet action and have led to the concept that antiplatelet agents exert their antiinflammatory actions via platelet-related mechanisms. 5 The ADP receptor P2Y12 was originally identified in platelets and in the brain. 6 It is a member of the P2 receptor family, which consists of the ion-channel P2X and the G-protein-coupled P2Y receptors. 7 P2 receptors are activated by the adenine nucleotides ATP and ADP, which can be released from platelets, endothelial cells, sympathetic nerve terminals, and immune cells. 8 P2 receptors have been shown to be involved in a variety of inflammatory processes, such as allergen-driven lung inflammation. 9 In addition, the P2Y12 receptor has been associated with enhanced cell growth in certain brain tumors. 10 Recently, P2Y12 was found to be expressed in vascular smooth muscle cells (SMC), 11 and a role in vessel contraction was suggested. 12 However, no functional changes were seen after thienopyridine tr...

show abstract

Thrombin- and Factor Xa–Induced DNA Synthesis Is Mediated by Transactivation of Fibroblast Growth Factor Receptor-1 in Human Vascular Smooth Muscle Cells

Cited by 75 publications

References 31 publications

Tissue factor is involved in retinoblastoma cell proliferation via both the Akt and extracellular signal-regulated kinase pathways

Tissue factor is involved in retinoblastoma cell proliferation via both the Akt and extracellular signal-regulated kinase pathways

From the Golgi–Cajal mapping to the transmitter-based characterization of the neuronal networks leading to two modes of brain communication: Wiring and volume transmission

Regulation of Functionally Active P2Y12 ADP Receptors by Thrombin in Human Smooth Muscle Cells and the Presence of P2Y12 in Carotid Artery Lesions

Contact Info

Product

Resources

About