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 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.
Abdulmalek
K
K
Critical Care and Respiratory Divisions, Royal Victoria Hospital, Montreal, Quebec H3A 1A1, Canada.
Ashur
F
F
Ezer
N
N
Ye
F
F
Magder
S
S
Hussain
S N
SN
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D015139:Blotting, Southern; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D042787:Receptor, TIE-2; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors
C117578:ANGPTL1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000091304:Angiopoietin-Like Protein 1; D000075802:Angiopoietin-like Proteins; D042682:Angiopoietins; C467629:Angpt1 protein, rat; D004268:DNA-Binding Proteins; C497444:Hif1a protein, rat; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; C105373:MEN1 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D042787:Receptor, TIE-2