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| 1 | Liver myofibroblasts activate protein C and respond to activated protein C显示文摘AIM:To study the protein C activation system in human liver myofibroblasts,and the effects of activated protein C(APC)on these cells.METHODS:Human liver myofibroblasts were obtained by outgrowth.Expression of protease activated receptor 1(PAR-1),endothelial protein C receptor(EPCR) and thrombomodulin(TM)was analyzed by flow cytometry.Extracellular signal-regulated kinase(ERK)1/2 activation was assessed by Western blotting using anti-phospho-ERK antibodies.Collagen synthesis was studied with real-time reverse transcription-polymerase chain reaction(RT-PCR).Activation of protein C was studied by incubating liver myofibroblasts with zymogen protein C in the presence of thrombin and detecting the generation of APC with a colorimetric assay using a peptide substrate. RESULTS:Primary cultures of human liver myofibroblasts expressed EPCR on their surface,together with PAR-1 and TM.This receptor system was functional since exposure of myofibroblasts to APC inducedERK1/2 phosphorylation in a dose-and time-dependent manner.Furthermore,APC significantly upregulated the expression of collagen mRNA,as shown by real-time RT-PCR.Collagen upregulation was controlled through the ERK pathway as it was inhibited when using the mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor PD98059.Finally,using a cell-based colorimetric assay,we showed that intact myofibroblasts converted protein C into APC in the presence of thrombin.CONCLUSION:These data suggest that APC is a new modulator of liver myofibroblast activity and contributes to the pathophysiology of chronic liver diseases. | Jennifer Gillibert-Duplantier Anne Rullier Véronique Neaud Walter Kisiel Jean Rosenbaum | 2010 | World Journal of Gastroenterology2010，16，2： | 2 |
| 2 | Thrombin up-regulates tissue factor pathway inhibitor-2 synthesis through eyclooxygenase-2-dependent,epidermal growth factor receptor-independent mechanism 显示文摘 | Neaud V Duplantier JG Mazzoeco C | 2004 | J Biol Chem2004，279，7： | 1 |
| 3 | Human hepatic myofibrob lasts increase invasiveres of hepatocellular carcinoma cells:evidence for a role of hepatocyte growth factor 显示文摘 | Neaud V Faouzi S Guirouilh J | 1997 | Hepatology1997，26，6： | 1 |
| 4 | Paradoxical pro-invasive effect of the serine proteinase inhibitor tissue factor pathway inhibitar-2 on human hepatocelluar carcinoma cells 显示文摘 | Neaud V Hisaka T Monvoisin A | 2000 | J Biochem2000，275，35： | 1 |
| 5 | Direct evidence that hepatocyte growth factor induced invasion of hepatocellular carcinoma cells is mediated by urokinase显示文摘 | Monvoisin A Neaud V De Ledinghen V | 1999 | J Hapatol1999，30，： | 1 |
| 6 | Thrombin up-regulates tissue factor pathway inhibitor-2 synthesis through a cyclooxygenase-2-dependent, epidermal growth factor receptor-independent mechanism显示文摘 | Neaud V Duplantier J G Mazzocco C | 2004 | Blood2004，279，7： | 1 |
| 7 | 显示文摘 | Faouzi S Le Bail B Neaud V | 1999 | Hepatology1999，30，： | 1 |
| 8 | Thrombin upregulates tissue factor pathway inhibitor-2 synthesis through a cyclooxygenase-2-dependent, epidermal growth factor receptor-independent mechanism 显示文摘 | Neaud V Duplantier JG Mazzocco C | 2004 | J Biol Chem2004，279，7： | 1 |
| 9 | Thrombin up-regu-latestissue factor pathway inhibitor-2 synthesis through a cyclooxygenase-2-dependent,epidermal growth factor receptor-independent mechanism显示文摘 | Neaud V Duplantier J G Mazzocco C | 2004 | Blood2004，279，7： | 1 |
| 10 | Paradoxical proinvasive effect of the serine proteinase inhibitor tissue factor pathway inhibitor-2 on human hepatocelluar carcinoma cells显示文摘 | Neaud V Hisaka T Monvoisin A | 2000 | J Biochem2000，275，35： | 1 |
| 11 | Myofibroblasts are responsible for collagen synthesis in the stroma of human hepatocellular carcinoma: an in vivo and in vitro study显示文摘 | Faouzi S Bail BL Neaud V | 1999 | J Hepatol1999，30，2： | 1 |
| 12 | Thrombin upregulates tissue factor pathway inhibitor-2 synthesis through a cyclooxygenase-2-dependent,epidermal growth factor receptor indepndent mechanism显示文摘 | NEAUD V DUPLANTIER JG MAZZOCCO C | 2004 | J Biol Chem2004，279，7： | 1 |
| 13 | Human hepatic myofibroblasts increase invasiveness of hepatocellular carcinoma cells:evidence for a role of hepatocyte growth factor显示文摘 | Neaud V Faouzi S Guirouilh J | 1997 | Hepatology1997，26，6： | 1 |
| 14 | Paradoxical pro-invasive effect of the serine proteinase inhibitor tissue factor pathway inhibitor-2 on human hepatocellular carcinoma cells显示文摘 | Neaud V Hisaka T Monvoisin A | 2000 | J Biol Chem2000，275，35： | 1 |
| 15 | Paradoxical pro-invasire effect of the serine proteinase inhibitor tissue factor pathway inhibitor-2 on human hepatocellular carcinoma cells显示文摘 | Neaud V Hisaka T Monvoisin A | 2000 | J Biol Chem2000，275，35： | 1 |
| 16 | Paradoxical proinvasive effect of the serine proteinase inhibitor tissue factor pathway inhibitor-2 on human hepatocelluar carcinoma cells显示文摘 | Neaud V Hisaka T Monvoisin A | 2000 | J Biol Chem2000，275，35： | 1 |
| 17 | Thrombin up-regulates tissue factor pathway inhibitor-2 synthesis through a cyclooxygenase-2-dependent, epidermal growth factor receptor-independent mechanism显示文摘 | Neaud V Duplantier JG Mazzocco C | 2004 | J Biol Chem2004，279，7： | 1 |
| 18 | Paradoxical pro-invasive effect of the serine proteinase inhibitor tissue factor pathway inhibitor-2 on human hepatocelluar carcinoma cells 显示文摘 | Neaud V Hisaka T Monvoisin A | 2000 | J Biochem2000，275，35： | 1 |
| 19 | Thrombin up-regulates tissue factor pathway inhibitor-2 synthesis through a cyclooxygenase-2-depent, epidermal growth factor receptor-independent mechanism显示文摘 | Neaud V Duplantier JG Mazzocco C | 2004 | J Biol Chem2004，279，20： | 1 |
| 20 | Paradoxical pro invasire effect of the serine proteinase inhibitor tissue factor path way inhibitor 2 on human hepato elluar carcinoma cells显示文摘 | Neaud V Hisaka T Monvoisin A | 2000 | ] Biol Chem2000，275，35： | 1 |
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