Neuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3

Xu, Yunling; Yuan, Lili; Mak, Judy; Pardanaud, Luc; Caunt, Maresa; Kasman, Ian; Larrivée, Bruno; Toro, R.; Suchting, Steven; Medvinsky, Alexander; Silva, Jillian; Yang, Jian; Thomas, Jean‐Léon; Koch, Alexander W.; Alitalo, Kari; Eichmann, Anne; Bagri, Anil

doi:10.1083/jcb.200903137

Cited by 308 publications

(203 citation statements)

References 56 publications

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“…Total RNA was isolated by extraction using a commercial kit (Macherey-Nagel, Germany, Nucleospin RNA II). Reverse transcription, real-time quantitative PCR (in triplicate) and analysis were performed as described previously (18). Vegfa, vegfr2, and Cav-1 genes were detected using QuantiTect primer assays (Qiagen).…”

Section: Methodsmentioning

confidence: 99%

Alteration of Developmental and Pathological Retinal Angiogenesis in angptl4-deficient Mice

Perdiguero

Galaup

Durand

et al. 2011

Journal of Biological Chemistry

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Proper vessel maturation, remodeling of endothelial junctions, and recruitment of perivascular cells is crucial for establishing and maintaining vessel functions. In proliferative retinopathies, hypoxia-induced angiogenesis is associated with disruption of the vascular barrier, edema, and vision loss. Therefore, identifying factors that regulate vascular maturation is critical to target pathological angiogenesis. Given the conflicting role of angiopoietin-like-4 (ANGPTL4) reported in the current literature using gain of function systems both in vitro and in vivo, the goal of this study was to characterize angiogenesis, focusing on perinatal retinal vascularization and pathological circumstances in angpl4-deficient mice. We report altered organization of endothelial junctions and pericyte coverage, both leading to impaired angiogenesis and increased vascular leakage that were eventually caught up, suggesting a delay in vessel maturation. In a model of oxygen-induced retinopathy, pathological neovascularization, which results from tissue hypoxia, was also strongly inhibited in angptl4-deficient mice. This study therefore shows that ANGPTL4 tunes endothelial cell junction organization and pericyte coverage and controls vascular permeability and angiogenesis, both during development and in pathological conditions.

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Section: Methodsmentioning

confidence: 99%

Alteration of Developmental and Pathological Retinal Angiogenesis in angptl4-deficient Mice

Perdiguero

Galaup

Durand

et al. 2011

Journal of Biological Chemistry

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“…88 Interestingly, NRP2 can bind not only VEGFC and VEGFD but also VEGF, simultaneously with VEGFR2 or VEGFR3 in vitro. 41,89,90 Nrp2 and Vegfr3 compound heterozygotes, but not Nrp2 and Vegfr2 compound heterozygotes, display defective lymphatic vascular development, 91 indicating that in vivo, NRP2 genetically interacts with VEGFR3, but not with VEGFR2. Thus, NRP2 functions as a coreceptor for VEGFR3 and may cooperate to increase the affinity of LECs toward VEGFC/D to enable maximal sensing of growth factor gradients.…”

Section: Circulation Research February 5 2016mentioning

confidence: 99%

Lymphatic System in Cardiovascular Medicine

Aspelund

Robciuc

Karaman³

et al. 2016

Circulation Research

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258

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Abstract:The mammalian circulatory system comprises both the cardiovascular system and the lymphatic system. In contrast to the blood vascular circulation, the lymphatic system forms a unidirectional transit pathway from the extracellular space to the venous system. It actively regulates tissue fluid homeostasis, absorption of gastrointestinal lipids, and trafficking of antigen-presenting cells and lymphocytes to lymphoid organs and on to the systemic circulation. The cardinal manifestation of lymphatic malfunction is lymphedema. Recent research has implicated the lymphatic system in the pathogenesis of cardiovascular diseases including obesity and metabolic disease, dyslipidemia, inflammation, atherosclerosis, hypertension, and myocardial infarction. Here, we review the most recent advances in the field of lymphatic vascular biology, with a focus on cardiovascular disease.

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“…52 Similarly, neuropilin-2 interacts with the VEGF-C tyrosine-kinase receptor VEGFR-3 and is crucial for the transduction of VEGF-C induced pro-lymphangiogenic signals. 55,66,67 The neuropilins were found to form complexes and modulate signal transduction mediated by several additional receptors including TGFb receptors, 68 platelet derived growth factor (PDGF) receptors, 69 Neurotrophin receptors, 70 the epidermal growth factor (EGF) receptor 71 and the hepatocyte growth factor receptor 72 (Fig. 3).…”

Section: Neuropilinsmentioning

confidence: 99%

The role of the semaphorins in cancer

Neufeld

Mumblat

Smolkin

et al. 2016

Cell Adhesion & Migration

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The semaphorins were initially characterized as axon guidance factors, but have subsequently been implicated also in the regulation of immune responses, angiogenesis, organ formation, and a variety of additional physiological and developmental functions. The semaphorin family contains more then 20 genes divided into 7 subfamilies, all of which contain the signature sema domain. The semaphorins transduce signals by binding to receptors belonging to the neuropilin or plexin families. Additional receptors which form complexes with these primary semaphorin receptors are also frequently involved in semaphorin signaling. Recent evidence suggests that semaphorins also fulfill important roles in the etiology of multiple forms of cancer. Some semaphorins have been found to function as bona-fide tumor suppressors and to inhibit tumor progression by various mechanisms while other semaphorins function as inducers and promoters of tumor progression. The semaphorin familyThe semaphorin family members are divided into 8 subclasses of which subclasses 1 and 2 contain invertebrate semaphorins while subclasses 3-7 contain the 22 vertebrate semaphorins. The 8th subclass contains viral semaphorins. In early publications, semaphorins were assigned confusing names. This situation was rectified by the adoption of a unified nomenclature in which sema is followed by the subclass number and by alphabetic designation within the subclass.1 Semaphorins are characterized by the presence of a »500 amino-acids long sema domain located close to their N-termini which is also present in semaphorin receptors of the plexin family, and by a plexin-semaphorin-integrin (PSI) domain located downstream to the sema domain. The sema domain is essential for semaphorin activity and plays a role in the determination of the receptor binding specificity.2 The sema domains of several different semaphorins were characterized by X-ray crystallography revealing a b propeller topology.3-5 Different semaphorin subclasses are characterized by class specific structural motifs. Thus, the vertebrate semaphorins belonging to classes 3, 4 and 7 contain immunoglobulin like domains, class-5 semaphorins contain thrombospondin repeats and class-3 semaphorins contain a basic domain. Class-3 semaphorins are the only vertebrate semaphorins produced as secreted proteins while other vertebrate semaphorins are membrane anchored or trans-membrane proteins that can be further processed into soluble forms by proteolytic cleavage (Fig.

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Neuropilin-2 mediates VEGF-C–induced lymphatic sprouting together with VEGFR3

Abstract: If neuropilin-2 and the growth factor VEGF-C don’t come together, lymphatic vessels don’t branch apart.

Cited by 308 publications

References 56 publications

Alteration of Developmental and Pathological Retinal Angiogenesis in angptl4-deficient Mice

Alteration of Developmental and Pathological Retinal Angiogenesis in angptl4-deficient Mice

Lymphatic System in Cardiovascular Medicine

The role of the semaphorins in cancer

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