2,3,7,8-Tetrachlorodibenzo- p -dioxin (TCDD) induces plasminogen activator inhibitor-1 through an aryl hydrocarbon receptor-mediated pathway in mouse hepatoma cell lines

Jul 12, 2002Archives of toxicology

TCDD increases a blood clotting regulator through a specific receptor pathway in mouse liver cancer cells

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Abstract

TCDD increased PAI-1 levels in wild-type mouse liver cells, but not in mutant cells lacking specific receptors.

  • TCDD, a known carcinogen, alters the expression of numerous genes, including those involved in detoxification and cell signaling.
  • The induction of PAI-1 by TCDD was confirmed to require the presence of the aryl hydrocarbon receptor (AhR) and its partner Arnt.
  • Increased PAI-1 mRNA levels following cycloheximide treatment suggest that TCDD exerts a direct transcriptional effect rather than relying on other proteins.
  • Transfection studies showed that TCDD significantly boosted PAI-1 promoter activity in wild-type cells, indicating a direct regulatory mechanism.
  • AhR antagonists were able to block the TCDD-mediated increase in PAI-1 promoter activity, further supporting the involvement of the AhR-Arnt complex.
  • Analysis of the PAI-1 promoter revealed that TCDD-induced transcription operates through a mechanism distinct from that of TGF-beta.

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