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Thromb Haemost 1995; 73(05): 812-818
DOI: 10.1055/s-0038-1653873
Original Articles
Coagulation
Schattauer GmbH Stuttgart

Transforming Growth Factor Betal and Beta2 Induce Down-Modulation of Thrombomodulin in Human Umbilical Vein Endothelial Cells

Taro Ohji
1   Department of Pediatrics, University of Occupational and Environmental Health, School of Medicine, Kitakyushu City, Japan
,
Hajime Urano
1   Department of Pediatrics, University of Occupational and Environmental Health, School of Medicine, Kitakyushu City, Japan
,
Akira Shirahata
1   Department of Pediatrics, University of Occupational and Environmental Health, School of Medicine, Kitakyushu City, Japan
,
Minoru Yamagishi
1   Department of Pediatrics, University of Occupational and Environmental Health, School of Medicine, Kitakyushu City, Japan
,
Ken Higashi
2   Department of Biochemistry, University of Occupational and Environmental Health, School of Medicine, Kitakyushu City, Japan
,
Sadao Gotoh
2   Department of Biochemistry, University of Occupational and Environmental Health, School of Medicine, Kitakyushu City, Japan
,
Yuji Karasaki
2   Department of Biochemistry, University of Occupational and Environmental Health, School of Medicine, Kitakyushu City, Japan
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Publikationsverlauf

Received 11. Oktober 1994

Accepted after revision 06. Februar 1995

Publikationsdatum:
09. Juli 2018 (online)

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Summary

To investigate the effects of transforming growth factor-betas (TGF-βs) on endothelial anticoagulant activity, we assayed thrombomodulin (TM) activity and antigen levels of human umbilical vein endothelial cells (HUVECs) incubated with TGF-βs in vitro. TGF-β1 suppressed surface TM activity and surface TM antigen levels maximally 12 h after incubation in dose-dependent manners. TGF-β2 was almost equipotent with TGF-β1 for the suppression of them. Both TGF-βs suppressed total TM antigen level in HUVECs, and the time course of the suppression was similar to that of the cell surface TM antigen level. The maximal reductions of TM mRNA levels by TGF-βs were observed at several hours ahead of those observed in both surface and total TM antigen levels, suggesting that the TGF-β-mediated suppression of TM antigen of HUVECs is primarily regulated at the TM mRNA level. Our present work suggests that the down-modulation of TM level induced by TGF-βs in HUVECs contributes in vivo to promoting the thrombogenesis either at the sites of injury of vessel walls, such as atherosclerotic lesions where TGF-β1 is released from platelets, smooth muscle cells and monocytes, or at neovascular walls in tumors secreting TGF-β2.

 

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