Differential expression of Tie-2 receptors and angiopoietins in response to in vivo hypoxia in rats
Differential expression of Tie-2 receptors and angiopoietins in response to in vivo hypoxia in rats
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DOI：
10.1152/ajplung.2001.281.3.l582
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发表时间：
2001-09-01
影响因子：
4.9
通讯作者：
Hussain, SNA
中科院分区：
文献类型：
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作者：
Abdulmalek, K;Ashur, F;Hussain, SNA
在这项研究中，我们评估了体内缺氧对Tie-2受体和血管生成素在清醒大鼠各器官中表达的影响，并将这些影响与缺氧诱导因子-1（HIF-1）的表达相关联。采用RT-PCR和Southern印迹法扩增常氧和缺氧（吸入氧分数为9-10%，持续12或48 h）大鼠组织中血管生成素-1、-2和-3、Tie-2和HIF-1 α的mRNA表达。缺氧引起肺、肝、小脑和心脏中血管生成素-1 mRNA和Tie-2 mRNA、蛋白和磷酸化水平下降，但肾脏和膈肌中没有。相比之下，缺氧升高了小脑中血管生成素-2 mRNA的水平，以及肺、肾和膈肌中血管生成素-3 mRNA的水平。HIF-1 α mRNA在常氧大鼠的大部分器官中丰富，但在低氧大鼠的肾脏和膈肌中显著诱导。我们的结论是，在体内缺氧通过减少血管生成素-1和上调血管生成素-2和-3对血管生成素-1Tie-2受体途径的活性产生抑制作用。低氧大鼠肾脏和膈肌中促血管生成素-3的诱导可通过HIF-1转录因子介导。
In this study, we assessed the effects of in vivo hypoxia on the expression of Tie-2 receptors and angiopoietins in various organs of conscious rats and correlated these effects with the expression of hypoxia-inducible factor-1 (HIF-1). RT-PCR and Southern blotting were used to amplify mRNA expression of angiopoietin-1, -2, and -3, Tie-2, and HIF-1 alpha in tissues of normoxic and hypoxic (fraction of inspired oxygen of 9-10% for either 12 or 48 h) rats. Hypoxia provoked a decline in angiopoietin-1 mRNA and Tie-2 mRNA, protein, and phosphorylation levels in the lung, liver, cerebellum, and heart but not in the kidney and diaphragm. In comparison, hypoxia raised the levels of angiopoietin-2 mRNA in the cerebellum and angiopoietin-3 mRNA in the lung, kidney, and diaphragm. HIF-1 alpha mRNA was abundant in most organs of normoxic rats but was significantly induced in the kidney and diaphragm of hypoxic rats. We conclude that in vivo hypoxia exerts inhibitory effects on the activity of the angiopoietin-1Tie-2 receptor pathway through reduction of angiopoietin-1 and upregulation of angiopoietin-2 and -3. Induction of angiopoietin-3 in the kidney and diaphragm of hypoxic rats could be mediated through the HIF-1 transcription factor.