Rac regulates thrombin-induced tissue factor expression in pulmonary artery smooth muscle cells involving the nuclear factor-kappaB pathway

Antioxidants & Redox Signaling
Talija DjordjevicRachida S BelAiba

Abstract

Pulmonary hypertension is associated with enhanced thrombogenicity of the vessel wall contributing to vascular remodeling. However, the signaling mechanisms promoting this prothrombotic state are not resolved. Here we investigated the role of the GTPase Rac in the regulation of tissue factor (TF) expression and activity in response to thrombin in pulmonary artery smooth muscle cells (PASMC). TF mRNA and protein expression and surface procoagulant activity were increased by thrombin in PASMC. These responses were enhanced in the presence of the constitutively active Rac mutant RacG12V, but were abrogated in cells expressing dominant-negative RacT17N. Thrombin and RacG12V also increased human TF promoter activity primarily involving a sequence between -636 and -111 bp containing a distal, nuclear factor-kappaB (NFkappaB)-dependent enhancer element. Indeed, thrombin and RacG12V stimulated NFkappaB-dependent transcriptional activity, and overexpression of p50/p65 significantly increased human TF promoter activity. Moreover, in RacG12V-overexpressing cells, TF promoter activity was significantly decreased by coexpression of dominant-negative mutants of IkappaBalpha and IkappaBKalpha, which prevent NFkappaB activation. As enhanced NF...Continue Reading

References

Mar 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·N MackmanJ H Morrissey
Nov 3, 1995·The Journal of Biological Chemistry·A BierhausJ Greten
May 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·G C Parry, N Mackman
Sep 1, 1996·The Biochemical Journal·M SundaresanT Finkel
Feb 15, 1997·Genes & Development·R PeronaJ C Lacal
Jun 11, 1998·Blood Coagulation & Fibrinolysis : an International Journal in Haemostasis and Thrombosis·K L Hassell
Aug 6, 2000·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A GörlachV B Schini-Kerth
Jun 8, 2001·Circulation Research·C PattersonM S Runge
Oct 10, 2001·Clinics in Chest Medicine·R M TuderN F Voelkel
Oct 10, 2001·Clinics in Chest Medicine·P HerveG Simonneau
Nov 24, 2001·Trends in Cell Biology·A J Ridley
Jul 20, 2002·Methods in Enzymology·Olaf Herkert, Agnes Görlach
Oct 26, 2002·Free Radical Biology & Medicine·Carine MichielsMartine Raes
Nov 16, 2002·International Immunopharmacology·Tieli WangJian Jian Li

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Citations

Jul 10, 2004·Antioxidants & Redox Signaling·Agnes Görlach
Aug 24, 2005·Antioxidants & Redox Signaling·Agnes Görlach
Dec 17, 2009·Antioxidants & Redox Signaling·Andreas PetryAgnes Görlach
Oct 4, 2011·Molecular Biology of the Cell·Isabel DieboldAgnes Görlach
Nov 17, 2007·American Journal of Respiratory and Critical Care Medicine·Babe BakouboulaFlorence Toti
Jan 7, 2014·Antioxidants & Redox Signaling·Damir KračunAgnes Görlach
Sep 18, 2012·Vascular Pharmacology·Elisabeth M Storck, Beata Wojciak-Stothard
Dec 14, 2011·Free Radical Biology & Medicine·Peter R Kvietys, D Neil Granger
Sep 30, 2014·Cellular & Molecular Immunology·Arvind PandaySanjay Batra
May 4, 2016·Current Hypertension Reports·Jeffrey C RobinsonDavid B Badesch
Feb 23, 2018·Antioxidants & Redox Signaling·Andreas Petry, Agnes Görlach
Dec 25, 2004·Arteriosclerosis, Thrombosis, and Vascular Biology·Talija DjordjevicAgnes Görlach
Feb 3, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Steve BonelloAgnes Görlach
Jan 4, 2019·Arteriosclerosis, Thrombosis, and Vascular Biology·Wenying LiangY Eugene Chen
Jul 20, 2017·Scientific Reports·Verena ZollerPamela Fischer-Posovszky
Nov 26, 2013·International Journal of Molecular Medicine·Xue ZhangYi-Biao Wang

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