Disease relevance of Tek

• RESULTS: Using in situ hybridization analysis, Ang-1, Ang-2, and Tie2 mRNA expression was observed in the ganglion cell layer (GCL) and the inner nuclear layer (INL) [1].
• Tie2 protein increased 2.4-fold at 3 weeks and 2.8-fold at 4 weeks after the infarction [2].
• In the current study, the localization of Tie-1/Tie-2 mRNA and proteins were further investigated in the same focal ischemia model [3].
• 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) [4].
• Angiopoietin-1 (Ang-1), an endothelial cell growth factor with influences on blood vessel stabilization, has been recently reported to prevent apoptosis in a neuroblastoma cell line via a pathway dependent on Tie-2 receptor [5].

High impact information on Tek

• These data demonstrate a role for the Tie2 pathway in pathologic angiogenesis, suggesting that targeting this pathway may yield effective antiangiogenic agents for treatment of cancer and other angiogenic diseases [6].
• Tie2 is a novel receptor tyrosine kinase that is expressed almost exclusively by vascular endothelium [6].
• The effects of the drugs were evaluated by morphometric assessment of endothelial cell injury in H&E, trypan blue, and immunostained (TIE2/Tek) biopsy specimens [7].
• Tie2 (a.k.a Tek) is an endothelium-specific receptor tyrosine kinase known to play a role in tumor angiogenesis [8].
• Surprisingly, however, unlike Tie2-null mutant mice, mice deficient in signaling through this tyrosine residue show a normal association of perivascular cells with nascent blood vessels [9].

Chemical compound and disease context of Tek

• The purpose of this study was to evaluate the expression of Tie-2 and Ang-1 and -2 in an acetic acid-induced gastric ulcer healing process in rats [10].

Biological context of Tek

• At the time of peak elevation in Ang-2, Tie2 phosphorylation was found to be markedly increased, consistent with receptor activation [11].
• A pericyte-derived angiopoietin-1 multimeric complex induces occludin gene expression in brain capillary endothelial cells through Tie-2 activation in vitro [12].
• During embryonic development, the growth of blood vessels requires the coordinated activation of endothelial receptor tyrosine kinases (RTKs) such as vascular endothelial growth factor receptor-2 (VEGFR-2) and Tie-2 [13].
• The reverse transcription/polymerase chain reaction technique identified Tie-2 receptor mRNA in intact DRG and in Ang-1-stimulated DRG cell cultures, but not in a Schwann cell line or in primary astrocyte cultures [5].
• Angiopoietin-1 (Ang-1), a newly discovered ligand of the endothelial-specific tyrosine kinase receptor Tie-2, has been found to promote cell survival, vascular maturation, and stabilization [14].

Anatomical context of Tek

• Angiopoietin-1 and -2, the ligands for Tie-2, increased in cardiac myocytes subjected to cyclic stretch but were not affected by stretch in endothelial cells (EC) [15].
• Immunohistochemical studies also showed increased immunoreactivity of Ang2 and Tie2 in the jeopardized myocardium after ischaemia/reperfusion [16].
• Modulation of Tie2 receptor activity by angiopoietin ligands is crucial for angiogenesis, blood vessel maturation, and vascular endothelium integrity [2].
• Strikingly, some of the cells infiltrating the treated muscles were found positive for markers of activated endothelial precursors (VEGFR-2/KDR and Tie-2) and for c-kit, an antigen expressed by pluripotent bone marrow stem cells [17].
• In situ hybridization showed that, after 60-minute ischemia and 72-hour reperfusion, both Tie-1 and Tie-2 mRNA appeared as capillary-like structures in the ischemic middle cerebral artery (MCA) cortex [3].

Associations of Tek with chemical compounds

• Alterations in expression of angiopoietins and the Tie-2 receptor in the retina of streptozotocin induced diabetic rats [1].
• Angiopoietin2 and Tie2, but not angiopoietin1 mRNA were increased with ROP, and angiopoietin2 was reduced with PD123319 [18].
• Angiotensin II induces expression of the Tie2 receptor ligand, angiopoietin-2, in bovine retinal endothelial cells [19].
• Tie-2 is an endothelial cell-specific receptor tyrosine kinase involved in vascular maturation and remodeling [20].
• We also observed that tyrosine phosphorylation of Tie-2 receptors is significantly attenuated in ovariectomized rats treated with 17-beta-estradiol [21].

Regulatory relationships of Tek

• In conclusion, in vitro BBB model studies revealed that the pericyte-derived multimeric angiopoietin-1/Tie-2 pathway induces occludin expression [12].
• We conclude that Ang-1 promotes neurite outgrowth from DRG cells positive for Tie-2 receptor [5].

Other interactions of Tek

• RESULTS: Diabetes was associated with increased gene and protein expression of VEGF, VEGF-R2, Ang-1, Ang-2 and Tie-2 [22].
• However, Tie-2 and Tie-1 protein levels increased in RCMEC [15].
• DITPA stimulates bFGF, VEGF, angiopoietin, and Tie-2 and facilitates coronary arteriolar growth [23].
• Stroke rats treated with DETA-NONOate show significantly increased Ang1, Tie2 and Occludin expression in the ischemic border compared with control stroke animals (p < 0.05) [24].
• 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 [4].

Analytical, diagnostic and therapeutic context of Tek

• Tie2 protein increased immediately after relief of ischaemia, and showed a significant increase from 6 h to 72 h after reperfusion as compared with the sham control [16].
• METHODS: In situ hybridization, reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analyses were performed to determine the mRNA and protein content for Ang-1 and Ang-2 and the Tie2 receptor in the retinas of STZ diabetic and age matched control rats [1].
• Immunoprecipitation of rat brain proteins with Tie-2 C-terminal antisera, however, produced a single spot of approximately 55-kDa pI approximately 5 by two-dimensional (2D) electrophoresis, which was identified as beta-tubulin by mass spectrometry [25].
• Western blot analysis revealed that Tie-2 expression reached a maximum on the third to fifth days [10].
• In accordance with these in vitro findings, immunohistochemistry revealed focal upregulation of Tie2 in capillaries at the border of infarcted human and rat myocardium [26].

References