Department of Pharmacology and Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Biochem Biophys Res Commun. 2013 Jul 12;436(4):691-7. doi: 10.1016/j.bbrc.2013.06.018. Epub 2013 Jun 14.
Despite the altered expression of Tie receptors and angiopoietin ligands during hypoxic conditions, the effect of hypoxia on Tie-mediated endothelial responses has not been elucidated. In this study, we found that hypoxia increased Tie receptor expression but attenuated angiopoietin-1 (Ang1)-induced Tie2 activity, including Tie2 phosphorylation, Tie2 downstream signaling activation, and endothelial cell tube formation. However, Ang1 binding to endothelial cells was increased during hypoxic conditions. We demonstrated that Tie1 suppression restored the Tie2 activity and that Tie1-mediated Tie2 suppression was independent of tyrosine phosphatase activity. These results suggest that under hypoxic conditions, Tie1 is critical for reducing Ang1-induced Tie2 activity and angiogenesis.
尽管在缺氧条件下 Tie 受体和血管生成素配体的表达发生了改变，但缺氧对 Tie 介导的内皮反应的影响尚未阐明。在这项研究中，我们发现缺氧增加了 Tie 受体的表达，但减弱了血管生成素-1（Ang1）诱导的 Tie2 活性，包括 Tie2 磷酸化、Tie2 下游信号激活和内皮细胞管状形成。然而，在缺氧条件下，Ang1 与内皮细胞的结合增加了。我们证明了 Tie1 的抑制恢复了 Tie2 的活性，并且 Tie1 介导的 Tie2 抑制与酪氨酸磷酸酶活性无关。这些结果表明，在缺氧条件下，Tie1 对于降低 Ang1 诱导的 Tie2 活性和血管生成至关重要。
