Angiopoietin-1 negatively regulates expression and activity of tissue factor in endothelial cells

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Normally, tissue factor (TF) is not expressed on the surface of endothelial cells, but its expression can be induced by vascular endothelial growth factor (VEGF) and tumor necrosis factor (TNF)-alpha. However, the signaling pathway(s) affecting this induction is unknown. Using human umbilical vein endothelial cells, we found that inhibitors of guanine-cytosine-rich DNA binding protein and nuclear factor (NF)-kappaB suppressed VEGF- and TNF-alpha -induced expression and activity of TF. However, unexpectedly, phosphatidylinositol (PI) 3'-kinase inhibitor enhanced the VEGF- and TNF-alpha -induced expression and activity of TF. Angiopoietin-1 (Ang1), a strong activator of intracellular PI 3'-kinase/Akt, inhibited the induction of TF by VEGF and TNF-alpha, whereas Ang1 itself did not produce any significant effect on TF. Selective activation (or inactivation) of PI 3'-kinase/Akt by using adenoviral transfer reduced (or enhanced) TNF-alpha -induced expression of TF mRNA and protein, regardless of Ang1 treatment. From these results, we conclude that Ang1 inhibits the up-regulation of TF expression, possibly through activation of PI 3'-kinase/Akt in endothelial cells. Ang1 may be useful as an inhibitor of VEGF- and TNF-alpha -induced coagulation, inflammation, and cancer progression.
Publisher
FEDERATION AMER SOC EXP BIOL
Issue Date
2002-01
Language
English
Article Type
Article
Keywords

NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; SIGNAL-TRANSDUCTION PATHWAY; BLOOD-VESSEL DEVELOPMENT; SERINE-THREONINE KINASE; GROWTH-FACTOR; OVEREXPRESSING ANGIOPOIETIN-1; VASCULAR-PERMEABILITY; TIE2 RECEPTOR; FACTOR GENE

Citation

FASEB JOURNAL, v.16, no.1, pp.126 - 126

ISSN
0892-6638
DOI
10.1096/fj.01-0556fje
URI
http://hdl.handle.net/10203/85526
Appears in Collection
MSE-Journal Papers(저널논문)
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