Differential expression of Tie-2 receptors and angiopoietins in response to in vivo hypoxia in rats

Abstract

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-1α 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-1α 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.