Induction of angiopoietin and Tie receptor mRNA expression after cerebral ischemia-reperfusion.
The angiopoietin/Tie receptor system may contribute to angiogenesis and vascular remodeling by mediating interactions of endothelial cells with smooth muscle cells and pericytes. The temporal expression of angiopoietin-1 (Angpo-1), angiopoietin-2 (Angpo-2), Tie-1, and Tie-2 mRNA was studied in a focal cerebral ischemia model in rats. The cDNA fragments obtained from reverse transcription polymerase chain reaction amplification were cloned and used as a probe to detect individual genes. Northern blot analysis showed a delayed increase of a 4.4-kb Angpo-1 transcript for up to 2 weeks after ischemia, eightfold higher than the values of the sham-operated controls. A biphasic expression of a 2.4-kb Angpo-2 transcript was noted, peaking at 24 hours (6.4-fold) and 2 weeks (4.6-fold) after ischemia. The expression of Tie-2 mRNA (4.3 kb), a receptor for Angpo-1, and Tie-1 mRNA (4.3 kb) also increased starting 24 hours after reperfusion and remained elevated for up to 2 weeks after ischemia. The temporal profiles of the expression of these genes were different from those of other angiogenic genes such as basic fibrobast growth factor/fibroblast growth factor receptor and vascular endothelial growth factor/vascular endothelial growth factor receptor and proteolytic enzymes (tissue-type plasminogen activator and urokinase plasminogen activator) and their inhibitors (plasminogen activator inhibitor-1). The expression patterns of these genes could be related to progressive tissue liquefaction and neovascularization after ischemia in this stroke model. Differential expression of these angiogenesis genes suggests the involvement of complex regulatory mechanisms that remain to be characterized.
Lin
T N
TN
Neuroscience Division, Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Wang
C K
CK
Cheung
W M
WM
Hsu
C Y
CY
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000098:blood supply / Q000201:enzymology; D017931:DNA Primers; D016228:Endothelial Growth Factors / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D008222:Lymphokines / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D018919:Neovascularization, Physiologic / Q000502:physiology; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D011956:Receptors, Cell Surface / Q000235:genetics*; D042764:Receptors, TIE; D015427:Reperfusion Injury / Q000378:metabolism*; D020521:Stroke / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467629:Angpt1 protein, rat; D017931:DNA Primers; D016228:Endothelial Growth Factors; D008222:Lymphokines; D008562:Membrane Glycoproteins; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D020794:Receptor Protein-Tyrosine Kinases; D042810:Receptor, TIE-1; D042787:Receptor, TIE-2; D042764:Receptors, TIE; D010959:Tissue Plasminogen Activator