Angiopoietin-1 negatively regulates expression and activity of tissue factor in endothelial cells
Angiopoietin-1 negatively regulates expression and activity of tissue factor in endothelial cells
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DOI：
10.1096/fj.01-0556fje
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发表时间：
2001-11-01
期刊：
影响因子：
4.8
通讯作者：
Koh, GY
中科院分区：
文献类型：
--
作者：
Kim, I;Oh, JL;Koh, GY
正常情况下，组织因子（TF）不在内皮细胞表面表达，但其表达可由血管内皮生长因子（VEGF）和肿瘤坏死因子（TNF）-α诱导。然而，影响这种诱导的信号通路是未知的。使用人脐静脉内皮细胞，我们发现富含鸟嘌呤-胞嘧啶的DNA结合蛋白和核因子（NF）-κ B抑制剂抑制VEGF和TNF-α诱导的TF表达和活性。然而，出乎意料的是，磷脂酰肌醇（PI）3 '-激酶抑制剂增强了VEGF和TNF-α诱导的TF表达和活性。血管生成素-1（Ang 1）是细胞内PI 3 '-激酶/Akt的强激活剂，可抑制VEGF和TNF-α对TF的诱导，而Ang 1本身对TF无明显影响。通过使用腺病毒转移选择性激活（或失活）PI 3 '-激酶/Akt降低（或增强）TNF-α诱导的TF mRNA和蛋白质表达，而与Ang 1处理无关。根据这些结果，我们得出结论，Ang 1抑制TF表达的上调，可能通过激活内皮细胞中的PI 3 '-激酶/Akt。Ang 1可用作VEGF和TNF-α诱导的凝血、炎症和癌症进展的抑制剂。
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.