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

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 a nd correlated these effects with the expression of hypoxia-inducible factor -1 (HIF-1). RT-PCR and Southern blotting were used to amplify mRNA expressi on of angiopoietin-1, -2, and -3, Tie-2, and HIF-1 alpha in tissues of norm oxic 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 hea rt but not in the kidney and diaphragm. In comparison, hypoxia raised the l evels of angiopoietin-2 mRNA in the cerebellum and angiopoietin-3 mRNA in t he lung, kidney, and diaphragm. HIF-1 alpha mRNA was abundant in most organ s of normoxic rats but was significantly induced in the kidney and diaphrag m of hypoxic rats. We conclude that in vivo hypoxia exerts inhibitory effec ts on the activity of the angiopoietin-1Tie-2 receptor pathway through redu ction of angiopoietin-1 and upregulation of angiopoietin-2 and -3. Inductio n of angiopoietin-3 in the kidney and diaphragm of hypoxic rats could be me diated through the HIF-1 transcription factor.