Angiopoietin-1/Tie2 Signal Augments Basal Notch Signal Controlling Vascular Quiescence by Inducing Delta-Like 4 Expression through AKT-mediated Activation of β-Catenin

Zhang, Jianghui; Fukuhara, Shigetomo; Sako, Keisuke; Takenouchi, Takato; Kitani, Hiroshi; Kume, Tsutomu; Koh, Gou Young; Mochizuki, Naoki

doi:10.1074/jbc.m110.192641

Cited by 105 publications

(95 citation statements)

References 52 publications

(65 reference statements)

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“…For example, pericyte marker expression in cells cultured from bone marrow increases with notch signalling (Stewart et al, 2011), and a recent study suggested that the stabilising effect of ANG1/TIE2 signalling between pericytes and ECs is mediated via induction of DLL4 expression in ECs (Fig. 5) (Zhang et al, 2011). However, the full relevance of these observations for pericyte-mediated stability in vivo remains unclear, as previous studies reported no defects in pericyte recruitment in DLL4-deficient mice.…”

Section: Network Formation: Remodelling and Maturationcontrasting

confidence: 42%

“…The activation of DLL4/notch signalling in ECs has a vessel stabilising effect via inhibition of angiogenic sprouting (Hellstrom et al, 2007;Leslie et al, 2007;Lobov et al, 2007;Siekmann and Lawson, 2007;Suchting et al, 2007). Notch signalling also promotes vascular stabilisation more directly through the induction of notchregulated ankyrin repeat protein (NRARP) expression (Phng et al, 2009) and via the production of ECM components (Benedito et al, 2008;Trindade et al, 2008;Zhang et al, 2011). NRARP limits notch signalling and promotes WNT/CTNNB1 signalling in stalk cells, which supports vascular stability and prevents EC retraction by inducing proliferation and improving intercellular junctions (Fig.…”

Section: Network Formation: Remodelling and Maturationmentioning

confidence: 99%

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Coordinating cell behaviour during blood vessel formation

2011

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SummaryThe correct development of blood vessels is crucial for all aspects of tissue growth and physiology in vertebrates. The formation of an elaborate hierarchically branched network of endothelial tubes, through either angiogenesis or vasculogenesis, relies on a series of coordinated morphogenic events, but how individual endothelial cells adopt specific phenotypes and how they coordinate their behaviour during vascular patterning is unclear. Recent progress in our understanding of blood vessel formation has been driven by advanced imaging techniques and detailed analyses that have used a combination of powerful in vitro, in vivo and in silico model systems. Here, we summarise these models and discuss their advantages and disadvantages. We then review the different stages of blood vessel development, highlighting the cellular mechanisms and molecular players involved at each step and focusing on cell specification and coordination within the network.

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Section: Network Formation: Remodelling and Maturationcontrasting

confidence: 42%

Section: Network Formation: Remodelling and Maturationmentioning

confidence: 99%

Coordinating cell behaviour during blood vessel formation

2011

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“…Notch and VEGF pathway interactions have been thoroughly studied in retinal sprouting angiogenesis, but only 1 study thus far has analyzed the Dll4/Notch crosstalk with angiopoietin/ Tie2 signaling (53). We showed here that Dll4/Notch signals were tumor cell survival.…”

Section: Discussionmentioning

confidence: 64%

Tie1 deletion inhibits tumor growth and improves angiopoietin antagonist therapy

D’Amico¹,

Korhonen²,

Anisimov³

et al. 2014

J. Clin. Invest.

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The endothelial Tie1 receptor is ligand-less, but interacts with the Tie2 receptor for angiopoietins (Angpt). Angpt2 is expressed in tumor blood vessels, and its blockade inhibits tumor angiogenesis. Here we found that Tie1 deletion from the endothelium of adult mice inhibits tumor angiogenesis and growth by decreasing endothelial cell survival in tumor vessels, without affecting normal vasculature. Treatment with VEGF or VEGFR-2 blocking antibodies similarly reduced tumor angiogenesis and growth; however, no additive inhibition was obtained by targeting both Tie1 and VEGF/VEGFR-2. In contrast, treatment of Tie1-deficient mice with a soluble form of the extracellular domain of Tie2, which blocks Angpt activity, resulted in additive inhibition of tumor growth. Notably, Tie1 deletion decreased sprouting angiogenesis and increased Notch pathway activity in the postnatal retinal vasculature, while pharmacological Notch suppression in the absence of Tie1 promoted retinal hypervasularization. Moreover, substantial additive inhibition of the retinal vascular front migration was observed when Angpt2 blocking antibodies were administered to Tie1-deficient pups. Thus, Tie1 regulates tumor angiogenesis, postnatal sprouting angiogenesis, and endothelial cell survival, which are controlled by VEGF, Angpt, and Notch signals. Our results suggest that targeting Tie1 in combination with Angpt/Tie2 has the potential to improve antiangiogenic therapy.

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“…Notch-regulated ankyrin repeat protein acts as a molecular link between the Notch and Wnt/β-catenin pathways in ECs (Phng et al, 2009). Furthermore, the Wnt/β-catenin pathway potentiates Notch signaling by inducing the expression of Dll4, which modulates vascular remodeling and arterial EC specification during early development (Corada et al, 2010;Yamamizu et al, 2010;Zhang et al, 2011). However, a recent report indicated that Dll4 expression in ECs and subsequent arterial specification are not mediated by the Wnt/β-catenin pathway in vivo (Wythe et al, 2013).…”

Section: Introductionmentioning

confidence: 98%

β-catenin-dependent transcription is central to Bmp-mediated formation of venous vessels

et al. 2015

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β-catenin regulates the transcription of genes involved in diverse biological processes, including embryogenesis, tissue homeostasis and regeneration. Endothelial cell (EC)-specific gene-targeting analyses in mice have revealed that β-catenin is required for vascular development. However, the precise function of β-cateninmediated gene regulation in vascular development is not well understood, since β-catenin regulates not only gene expression but also the formation of cell-cell junctions. To address this question, we have developed a novel transgenic zebrafish line that allows the visualization of β-catenin transcriptional activity specifically in ECs and discovered that β-catenin-dependent transcription is central to the bone morphogenetic protein (Bmp)-mediated formation of venous vessels. During caudal vein (CV) formation, Bmp induces the expression of aggf1, a putative causative gene for KlippelTrenaunay syndrome, which is characterized by venous malformation and hypertrophy of bones and soft tissues. Subsequently, Aggf1 potentiates β-catenin transcriptional activity by acting as a transcriptional co-factor, suggesting that Bmp evokes β-catenin-mediated gene expression through Aggf1 expression. Bmp-mediated activation of β-catenin induces the expression of Nr2f2 (also known as Coup-TFII), a member of the nuclear receptor superfamily, to promote the differentiation of venous ECs, thereby contributing to CV formation. Furthermore, β-catenin stimulated by Bmp promotes the survival of venous ECs, but not that of arterial ECs. Collectively, these results indicate that Bmp-induced activation of β-catenin through Aggf1 regulates CV development by promoting the Nr2f2-dependent differentiation of venous ECs and their survival. This study demonstrates, for the first time, a crucial role of β-catenin-mediated gene expression in the development of venous vessels.

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Angiopoietin-1/Tie2 Signal Augments Basal Notch Signal Controlling Vascular Quiescence by Inducing Delta-Like 4 Expression through AKT-mediated Activation of β-Catenin

Cited by 105 publications

References 52 publications

Coordinating cell behaviour during blood vessel formation

Coordinating cell behaviour during blood vessel formation

Tie1 deletion inhibits tumor growth and improves angiopoietin antagonist therapy

β-catenin-dependent transcription is central to Bmp-mediated formation of venous vessels

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