Coagulation Factors VIIa and Xa Induce Cell Signaling Leading to Up-regulation of the egr-1 Gene

Camerer, Eric; Røttingen, John-Arne; Gjernes, Elisabet; Larsen, Kristin; Skartlien, Anne Helen; Iversen, Jens-Gustav; Prydz, Hans

doi:10.1074/jbc.274.45.32225

Cited by 167 publications

(200 citation statements)

References 41 publications

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“…Factor VIIa appeared to have no e ect. However, two recent studies by Camerer et al (1999Camerer et al ( , 2000 show that PAR2 can be activated by factor VIIa, but this occurs optimally only when the VIIa is bound to tissue factor (TF) on the cell surface and factor X is present. Under these conditions, factor VIIa (and Xa) activate PAR2 with an EC 50 of approximately 8 pM.…”

Section: Par2mentioning

confidence: 99%

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Protease activated receptors: theme and variations

Molino²,

et al. 2001

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The four PAR family members are G protein coupled receptors that are normally activated by proteolytic exposure of an occult tethered ligand. Three of the family members are thrombin receptors. The fourth (PAR2) is not activated by thrombin, but can be activated by other proteases, including trypsin, tryptase and Factor Xa. This review focuses on recent information about the manner in which signaling through these receptors is initiated and terminated, including evidence for inter-as well as intramolecular modes of activation, and continuing e orts to identify additional, biologicallyrelevant proteases that can activate PAR family members. Oncogene (2001) 20, 1570 ± 1581.

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Section: Par2mentioning

confidence: 99%

“…Factor Xa (Parry et al, 1996;Camerer et al, 2000). TF/VIIa (Camerer et al, 1999(Camerer et al, , 2000. MT-SP1 (Takeuchi et al, 2000).…”

Section: Which Receptor(s) Contribute To Thrombin Responses In Any Pamentioning

confidence: 99%

Protease activated receptors: theme and variations

Molino²,

et al. 2001

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“…Several reports support the hypothesis of a key role for coagulation factors in the pathogenesis of tissue fibrosis, particularly within the kidney (8,(27)(28)(29)(30). Interestingly, earlier works suggested that FXa, the enzymatically active constituent of the prothrombinase complex, triggers complex pathways involved in the regulation of cellular growth (31,32). Binding of FXa to vascular endothelial cells induces the release of PDGF-like molecules, thus providing a paracrine mechanism for cell proliferation (33).…”

mentioning

confidence: 99%

Protease-Activated Receptor-2 Expression in IgA Nephropathy

Grandaliano

Pontrelli²,

Cerullo³

et al. 2003

Journal of the American Society of Nephrology

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ABSTRACT. An increasing body of evidence suggests that proteases may play a key role in the pathogenesis of tissue fibrosis. Protease-activated receptor-2 (PAR-2) is cleaved and activated by trypsin-like proteolytic enzymes, including tryptase and activated coagulation factor X (FXa). Both these soluble mediators have been demonstrated, directly or indirectly, at the interstitial level in progressive renal diseases, including IgA nephropathy (IgAN). PAR-2 mRNA and protein levels were investigated by RT-PCR and immunohistochemistry, respectively, in 17 biopsies from IgAN patients and 10 normal kidneys. PAR-2 expression was also evaluated, by RT-PCR and western blotting, in cultured human mesangial and proximal tubular cells. Finally, gene expression of plasminogen activator inhibitor-1 (PAI-1) and TGF-β, two powerful fibrogenic factors, was evaluated in FXa-, trypsin-, and PAR-2 activating peptide-stimulated human proximal tubular cells by Northern blot. In normal kidneys, PAR-2 gene expression was barely detectable, whereas in IgAN biopsies the mRNA levels for this protease receptor were strikingly increased and directly correlated with the extent of interstitial fibrosis. Immunohistochemical staining demonstrated that PAR-2 protein expression in IgAN biopsies was mainly localized in the proximal tubuli and within the interstitial infiltrate. Proximal tubular cells in culture expressed PAR-2. Activation of this receptor by FXa in tubular cells induced a striking increase in intracellular calcium concentration. In addition, incubation of both cell lines with trypsin, FXa, or PAR-2 activating peptide caused a marked upregulation of PAI-1 gene expression that was not counterbalanced by an increased expression of plasminogen activators. Finally, PAR-2 activation induced a significant upregulation of TGF-β gene and protein expression in both mesangial and tubular cells. On the basis of our data, we can suggest that PAR-2 expressed by renal resident cells and activated by either mast cell tryptase or FXa may induce extracellular matrix deposition modifying the PAI-1/PA balance and inducing TGF-β expression. These molecular mechanisms may underlie interstitial fibrosis in IgAN. E-mail: g.grandaliano@nephro.uniba.it

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“…They found that 24 genes increased, including cfos, EGF, and IL 1. This activation of cytokine or oncogene could promote invasive ability and MMP expression, whereas MMPs could lead to a cancer cell's extracellular matrix degradation, thus participating in the regulation of cancer cell invasion (Camerer et al, 1999). Researchers have found that TF/FVIIa complex could inhibit the apoptosis of a baby hamster's kidney cells induced by serum deprivation by activating PI3K/ Akt signal transduction (Sorensen et al, 2003;Versteeg et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Effect of Tissue Factor on Invasion Inhibition and Apoptosis Inducing Effect of Oxaliplatin in Human Gastric Cancer Cell

Li²,

Hou³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Objective: Tissue factor (TF) is expressed abnormally in certain types of tumor cells, closely related to invasion and metastasis. The aim of this study was to construct a human gastric cancer cell line SGC7901 stably-transfected with human TF, and observe effects on oxaliplatin-dependent inhibition of invasion and the apoptosis induction. Methods: The target gene TF was obtained from human placenta by nested PCR and introduced into the human gastric cell line SGC7901 through transfection mediated by lipofectamine. Stably-transfected cells were screened using G418. Examples successfully transfected with TF-pcDNA3 recombinant (experimental group), and empty vector pcDNA3 (control group) were incubated with oxaliplatin. Transwell chambers were used to show change in invasive ability. Caspase-3 activity was detected using a colorimetric method and annexin-V/PI doublestaining was applied to detect apoptosis. Results: We generated the human gastric cancer cell line SGC7901/TF successfully, expressing TF stably and efficiently. Compared with the control group, invasion increased, whereas caspase-3 activity and apoptosis rate were decreased in the experimental group. Conclusion: TF can enhance the invasive capacity of gastric cancer cells in vitro. Its increased expression may reduce invasion inhibition and apoptosis-inducing effects of oxaliplatin and therefore may warrant targeting for improved chemotherapy.

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Coagulation Factors VIIa and Xa Induce Cell Signaling Leading to Up-regulation of the egr-1 Gene

Cited by 167 publications

References 41 publications

Protease activated receptors: theme and variations

Protease activated receptors: theme and variations

Protease-Activated Receptor-2 Expression in IgA Nephropathy

Effect of Tissue Factor on Invasion Inhibition and Apoptosis Inducing Effect of Oxaliplatin in Human Gastric Cancer Cell

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