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

被引:99
作者
Kim, I
Oh, JL
Ryu, YS
So, JN
Sessa, WC
Walsh, K
Koh, GY
机构
[1] Pohang Univ Sci & Technol, Dept Life Sci, Natl Creat Res Initiat Ctr Endothelial Cells, Pohang 790784, South Korea
[2] Pohang Univ Sci & Technol, Div Mol & Life Sci, Pohang 790784, South Korea
[3] Woosuk Univ, Dept Biotechnol, Chonju 560180, South Korea
[4] Yale Univ, Sch Med, Boyer Ctr Mol Med, Dept Pharmacol, New Haven, CT 06536 USA
[5] St Elizabeths Med Ctr Boston, Div Cardiovasc Res, Boston, MA 02135 USA
关键词
vascular endothelial growth factor; TNF-alpha; Akt; phosphatidylinositol 3 '-kinase;
D O I
10.1096/fj.01-0556fje
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
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页码:126 / +
页数:24
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