title: Plasminogen activator inhibitor 1 and 2 are tumor necrosis factor/cachectin-responsive genes.
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.
mesh_terms: D002460:Cell Line; D003001:Cloning, Molecular; D005354:Fibrosarcoma; D005796:Genes / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors; D015849:Plasminogen Inactivators; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D006023:Glycoproteins; D015849:Plasminogen Inactivators; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D010960:Plasminogen Activators