Transcriptional and post‐translation regulation of the Tiel receptor by fluid shear stress changes in vascular endothelial cells

Chen-Konak, Limor; Guetta-Shubin, Yulia; Yahav, Hava; Shay-Salit, Ayelet; Zilberman, Michal; Binah, Ofer; Resnick, Nitzan

doi:10.1096/fj.02-1151fje

Cited by 47 publications

(52 citation statements)

References 68 publications

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“…Microarray analysis of HUVEC gene expression under static and 2 Pa laminar shear stress showed CLEC14A and ROBO4 were markedly upregulated (significant false discovery rate of o12% and o1% respectively) in the absence of shear stress. Real-time PCR analysis confirmed the predicted downregulation of CLEC14A and ROBO4 expression (Figure 9a) in HUVEC exposed to 2 Pa of shear stress for 24 h. TIE1 is a validated marker of reduced shear stress at the endothelial surface (Chen-Konak et al, 2003;Porrat et al, 2004;Woo et al, 2011). Double immunofluorescence staining of TIE1 and CLEC14A showed that they co-localised on tumor vessels (Figure 9b).…”

Section: Clec14a and Vascular Development In Zebrafishsupporting

confidence: 54%

Identification and angiogenic role of the novel tumor endothelial marker CLEC14A

et al. 2011

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Section: Clec14a and Vascular Development In Zebrafishsupporting

confidence: 54%

Identification and angiogenic role of the novel tumor endothelial marker CLEC14A

et al. 2011

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“…Mechanosensors of shear stress in endothelial cells include integrins, G protein-coupled receptors, PECAM-1, and the membrane lipid layer (5). The most recent additions to the list of shear stress mediators are the members of the Tie family of receptor tyrosine kinases (9,10). A tyrosine kinase with immunoglobulin-like and EGF-like domains 1, Tie1 is expressed almost exclusively in endothelial cells (11).…”

Section: Introductionmentioning

confidence: 99%

Tie1 attenuation reduces murine atherosclerosis in a dose-dependent and shear stress–specific manner

Woo¹,

Qu²,

Babaev³

et al. 2011

J. Clin. Invest.

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Although the response of endothelial cells to the disturbed blood flow in the vicinity of atherosclerotic lesions is known to be distinct from that elicited by nonatherogenic laminar flow, the mechanisms involved are poorly understood. Our initial studies confirmed that expression of the endothelial receptor tyrosine kinase Tie1 was evident at regions of atherogenic flow in mature animals. We therefore hypothesized that Tie1 plays a role in the endothelial response to atherogenic shear stress. Consistent with this, we found that Tie1 +/-mice bred to the apoE-deficient background displayed a 35% reduction in atherosclerosis relative to Tie1 +/+ ;Apoe -/-mice. Since deletion of Tie1 results in embryonic lethality secondary to vascular dysfunction, we used conditional and inducible mutagenesis to study the effect of endothelial-specific Tie1 attenuation on atherogenesis in Apoe -/-mice and found a dose-dependent decrease in atherosclerotic lesions. Analysis of primary aortic endothelial cells indicated that atheroprotective laminar flow decreased Tie1 expression in vitro. Attenuation of Tie1 was associated with an increase in eNOS expression and Tie2 phosphorylation. In addition, Tie1 attenuation increased IkBα expression while decreasing ICAM levels. In summary, we have found that shear stress conditions that modulate atherogenic events also regulate Tie1 expression. Therefore, Tie1 may play a novel proinflammatory role in atherosclerosis.

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“…This process is stimulated by phorbol esters as well as the physiological activators VEGF, TNFα and changes in shear stress (16,18,28,29). Constitutive and activated cleavage of Tie1 is mediated by metalloprotease activity (17).…”

Section: Resultsmentioning

confidence: 99%

The receptor tyrosine kinase Tie1 is expressed and activated in epithelial tumour cell lines

Rees

Singh²,

Brindle³

2007

Int J Oncol

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Abstract. The receptor tyrosine kinase Tie1 is expressed primarily in vascular endothelial cells. The receptor has also been detected in epithelial tumours in breast, thyroid and gastric cancers and in tumour cell lines where it appears as a 45 kDa truncated receptor fragment. In this study, we show that in addition to truncated Tie1, breast and colon tumour cell lines express a full-length Tie1 holoreceptor. In contrast to the situation in endothelial cells, Tie1 truncation is not activated by phorbol esters and generation of truncated Tie1 does not occur via a metalloprotease-inhibitor sensitive mechanism. Examination of the phosphorylation status of Tie1 revealed both the holoreceptor and truncated receptor to be constitutively activated in MCF-7 cells. These data indicate that Tie1 expressed in epithelial tumour cell lines is present in holoreceptor and truncated forms, and in MCF-7 cells both forms are constitutively phosphorylated and competent to signal. Our findings suggest therefore that antiangiogenic strategies targeting the angiopoietin/Tie system in tumour microvasculature could also have additional direct effects on the tumour epithelial cells within those tumours in which there is also extravascular expression of the Tie1 receptor tyrosine kinase.

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Transcriptional and post‐translation regulation of the Tiel receptor by fluid shear stress changes in vascular endothelial cells

Cited by 47 publications

References 68 publications

Identification and angiogenic role of the novel tumor endothelial marker CLEC14A

Identification and angiogenic role of the novel tumor endothelial marker CLEC14A

Tie1 attenuation reduces murine atherosclerosis in a dose-dependent and shear stress–specific manner

The receptor tyrosine kinase Tie1 is expressed and activated in epithelial tumour cell lines

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