1. Cadmium induces plasminogen activator inhibitor-1 via Smad2/3 signaling pathway in human endothelial EA.hy926 cells
- Author
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Chika Yamamoto, Takato Hara, Toshiyuki Kaji, Miki Sakuma, and Tomoya Fujie
- Subjects
Umbilical Veins ,Cell Survival ,medicine.medical_treatment ,Smad2 Protein ,010501 environmental sciences ,Toxicology ,030226 pharmacology & pharmacy ,01 natural sciences ,Tissue plasminogen activator ,Cell Line ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Fibrinolysis ,Plasminogen Activator Inhibitor 1 ,medicine ,Humans ,Smad3 Protein ,Transcription factor ,0105 earth and related environmental sciences ,Endothelial Cells ,Cell biology ,Endothelial stem cell ,chemistry ,Coagulation ,Plasminogen activator inhibitor-1 ,Tissue Plasminogen Activator ,Signal transduction ,Plasminogen activator ,medicine.drug ,Cadmium ,Signal Transduction - Abstract
Modulation of the blood coagulation fibrinolytic system is an essential function of vascular endothelial cells. Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) are major fibrinolytic regulatory proteins synthesized by vascular endothelial cells; fibrinolytic activity is dependent on the balance between these proteins. Previously, we have reported that cadmium, an initiator of ischemic heart disease, induces PAI-1 expression and suppresses fibrinolytic activity in cultured human vascular endothelial cells. However, the key molecules involved in cadmium-induced PAI-1 induction remain unclear. Herein, we investigated the contribution of Smad2 and Smad3, transcriptional factors involved in PAI-1 induction via transforming growth factor-β, using the human vascular endothelial cell line EA.hy926 cells in culture. Our findings indicated that cadmium induces PAI-1 expression without affecting t-PA expression up to 20 µM, a non-cytotoxic concentration, and PAI-1 induction by cadmium is partly mediated via Smad2 and Smad3. This study provides a possible mechanism underlying cadmium-induced vascular disorders.
- Published
- 2021