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Plasminogen activator inhibitor 1 and 2 are tumor necrosis factor/cachectin-responsive genes
R L Medcalf1, E K Kruithof, W D Schleuning
1Central Hematology Laboratory, University of Lausanne Medical School, Switzerland.
Abstract:
Human rTNF/Cachectin was shown to stimulate gene transcription of plasminogen activator inhibitor (PA1)-1 and PAI-2, and simultaneously suppress constitutive gene expression of tissue-type plasminogen activator (t-PA) in human fibrosarcoma cells. We propose that a TNF-mediated reprogramming of gene transcription induces, in appropriate target cells, an anti-fibrinolytic state, which may cooperate with the induction of procoagulant activity (tissue factor) to stabilize the fibrin deposits commonly found in inflamed tissue. PAI genes also provide a model system for a study of the molecular pathways underlying TNF-mediated signal transduction.
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