Abdulmalek K, Ashur F, Ezer N, Ye F, Magder S, Hussain S N
Critical Care and Respiratory Divisions, Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada.
Am J Physiol Lung Cell Mol Physiol. 2001 Sep;281(3):L582-90. doi: 10.1152/ajplung.2001.281.3.L582.
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-1/Tie-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.
在本研究中，我们评估了体内缺氧对清醒大鼠各器官中Tie-2受体和血管生成素表达的影响，并将这些影响与缺氧诱导因子-1（HIF-1）的表达相关联。采用逆转录聚合酶链反应（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小时）大鼠组织中血管生成素-1、-2和-3、Tie-2以及HIF-1α的mRNA表达。缺氧导致肺、肝、小脑和心脏中血管生成素-1 mRNA以及Tie-2 mRNA、蛋白和磷酸化水平下降，但肾脏和膈肌未出现这种情况。相比之下，缺氧使小脑中血管生成素-2 mRNA水平升高，肺、肾脏和膈肌中血管生成素-3 mRNA水平升高。HIF-1α mRNA在常氧大鼠的大多数器官中含量丰富，但在缺氧大鼠的肾脏和膈肌中显著诱导表达。我们得出结论，体内缺氧通过降低血管生成素-1以及上调血管生成素-2和-3，对血管生成素-1/Tie-2受体途径的活性产生抑制作用。缺氧大鼠肾脏和膈肌中血管生成素-3的诱导可能通过HIF-1转录因子介导。
