联系方式:400-990-3999 / 邮箱:sales@xiyashiji.com
西亚试剂 —— 品质可靠,值得信赖
NF-κB Transcription Factor p50 Critically Regulates Tissue Factor in Deep Vein Thrombosis*
Yi-Dan Li1, Bu-Qing Ye1, Sheng-Xi Zheng, Jin-Tao Wang, Jian-Guo Wang, Ming Chen, Ji-Guo Liu, Xin-Hui Pei?, Li-Jing Wang||, Zhi-Xin Lin?, Kalpna Gupta**, Nigel Mackman, Arne Slungaard**, Nigel S. Key, and Jian-Guo Geng**2
From the Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Graduate School of Chinese Academy of Sciences, CAS, Shanghai 200031, China, the Division of Hematology/Oncology, University of North Carolina, Chapel Hill, North Carolina 27599, the ?College of Life Science & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China, the ||Institute of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, China, and the **Vascular Biology Center and Division of Hematology, Oncology and Transplantation, University of Minnesota Medical School, Minneapolis, Minnesota 55455
NF-B transcription factors regulate the expression of tissue factor (TF), a principal initiator of the coagulation cascade. Dominant among them is the p50/p65 heterodimer. Here we report that Andrographolide (Andro; a p50 inhibitor) and genetic deletion of p50 attenuated TF activity in stimulated endothelial cells and monocytes/macrophages. Results of the electrophoretic mobility "supershift" assay and chromatin immunoprecipitation demonstrated the direct interaction of the p50/p65 heterodimer with the NF-κB site of the human TF promoter. Andro-treated and p50 null mice both exhibited blunted TF expression and reduced venous thrombosis, which were recapitulated by an anti-murine TF antibody in vivo. Our findings thus indicate that regulation of TF by NF-κB transcription factor p50 is essential for the pathogenesis of deep vein thrombosis and suggest that specific inhibitors of p50, such as Andro, may be therapeutically valuable for preventing and perhaps treating venous thrombosis.