Devic E, Rizzoti K, Bodin S, Knibiehler B, Audigier Y.. Amino acid sequence and embryonic expression of msr/apj, the mouse homolog of Xenopus X-msr and human APJ. Mech Dev 84: 199-203

Unité INSERM U-397, CHU Rangueil, Toulouse, France.
Mechanisms of Development (Impact Factor: 2.44). 07/1999; 84(1-2):199-203. DOI: 10.1016/S0925-4773(99)00081-7
Source: PubMed


We have recently identified a new G protein-coupled receptor, X-msr, whose expression is associated with the endothelial lineage in Xenopus laevis (Devic, E., Paquereau, L., Vernier, P., Knibiehler, B., Audigier, Y., 1996. Expression of a new G protein-coupled receptor X-msr is associated with an endothelial lineage in Xenopus laevis. Mech. Dev. 59, 129-140). Based on its structural analogy to the human orphan receptor APJ, we cloned the murine msr/apj receptor and analyzed its expression in developing tissues. As observed for X-msr, msr/apj transcripts are detected in the endothelium of the primary blood vessels and the forming heart. In addition, they are expressed in somites, limb bud and branchial arches. This expression pattern is distinct from that of the Flk1 gene and suggests that the msr/apj gene is expressed in a subpopulation of endothelial precursors and a mesenchymal population derived from paraaxial mesoderm.

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Available from: Stéphane Bodin, Apr 09, 2015
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    • "Apelin has been recognized as the endogenous ligand of the human G protein–coupled receptor APJ [4], a member of the seven-transmembrane-receptor family. During embryonic development, APJ expression is largely restricted to the endothelial cells of the developing vascular system [5] and apelin is essential for vascular patterning of the embryo [6]. Nevertheless, apelin and its receptor are strongly expressed in the adult blood vasculature as well [7], and apelin was reported to stimulate blood endothelial cell growth in various in vitro [8, 9] and in vivo [6, 9] angiogenesis models. "
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    ABSTRACT: Whereas the role of the G-protein-coupled APJ receptor and its ligand, apelin, in angiogenesis has been well documented, the ability of the apelin/APJ system to induce lymphangiogenesis and lymphatic metastasis has been largely unexplored. To this end, we first show that APJ is expressed in lymphatic endothelial cells (LECs) and, moreover, that it responds to apelin by activating the apelinergic signaling cascade. We find that although apelin treatment does not influence the proliferation of LECs in vitro, it enhances their migration, protects them against UV irradiation-induced apoptosis, increases their spheroid numbers in 3D culture, stimulates their in vitro capillary-like tube formation and, furthermore, promotes the invasive growth of lymphatic microvessels in vivo in the matrigel plug assay. We also demonstrate that apelin overexpression in malignant cells is associated with accelerated in vivo tumor growth and with increased intratumoral lymphangiogenesis and lymph node metastasis. These results indicate that apelin induces lymphangiogenesis and, accordingly, plays an important role in lymphatic tumor progression. Our study does not only reveal apelin as a novel lymphangiogenic factor but might also open the door for the development of novel anticancer therapies targeting lymphangiogenesis.
    Full-text · Article · May 2014 · Oncotarget
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    • "F13A is an established antagonist of APJ receptor with a substitution of phenylalanine by alanine in the C-terminal of apelin-13. [17]. Therefore, to further assess the role of apelin in the maintenance of insulin sensitivity, 20 nmol/L F13A (Phoenix Pharmaceuticals, USA) was exposed to HepG2 cells and mouse primary hepatocytes treated with TNF-α or/and apelin. "
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    ABSTRACT: Apelin, a novel adipokine, is the specific endogenous ligand of G protein-coupled receptor APJ. Consistent with its putative role as an adipokine, apelin has been linked to states of insulin resistance. However, the function of apelin in hepatic insulin resistance, a vital part of insulin resistance, and its underlying mechanisms still remains unclear. Here we define the impacts of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes. Our studies indicate that apelin reversed TNF-α-induced reduction of glycogen synthesis in HepG2 cells, mouse primary hepatocytes and liver tissues of C57BL/6J mice by improving JNK-IRS1-AKT-GSK pathway. Moreover, Western blot revealed that APJ, but not apelin, expressed in the hepatocytes and liver tissues of mice. We found that F13A, a competitive antagonist for G protein-coupled receptor APJ, suppressed the effects of apelin on TNF-α-induced reduction of glycogen synthesis in the hepatocytes, suggesting APJ is involved in the function of apelin. In conclusion, we show novel evidence suggesting that apelin ameliorates TNF-α-induced reduction of glycogen synthesis in the hepatocytes through G protein-coupled receptor APJ. Apelin appears as a beneficial adipokine with anti-insulin resistance properties, and thus as a promising therapeutic target in metabolic disorders.
    Preview · Article · Aug 2013 · PLoS ONE
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    • "Adriamycin may inhibit growth of ECs; this would make this liposome appropriate for conjugation with apelin or APJ antibody. However, APJ is also weakly expressed by neuronal cells and cardiomyocytes [22], [23]. Therefore, it may be better to use EC-specific inhibitors such as tyrosine kinase inhibitors for VEGF receptors. "
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    ABSTRACT: A drug delivery system specifically targeting endothelial cells (ECs) in tumors is required to prevent normal blood vessels from being damaged by angiogenesis inhibitors. The purpose of this study was to investigate whether apelin, a ligand for APJ expressed in ECs when angiogenesis is taking place, can be used for targeting drug delivery to ECs in tumors. Uptake of apelin via APJ stably expressed in NIH-3T3 cells was investigated using TAMRA (fluorescent probe)-conjugated apelin. Both long and short forms of apelin (apelin 36 and apelin 13) were taken up, the latter more effectively. To improve efficacy of apelin- liposome conjugates, we introduced cysteine, with its sulfhydryl group, to the C terminus of apelin 13, resulting in the generation of apelin 14. In turn, apelin 14 was conjugated to rhodamine-encapsulating liposomes and administered to tumor-bearing mice. In the tumor microenvironment, we confirmed that liposomes were incorporated into the cytoplasm of ECs. In contrast, apelin non-conjugated liposomes were rarely found in the cytoplasm of ECs. Moreover, non-specific uptake of apelin-conjugated liposomes was rarely detected in other normal organs. ECs in normal organs express little APJ; however, upon hypoxic stimulation, such as in tumors, ECs start to express APJ. The present study suggests that apelin could represent a suitable tool to effectively deliver drugs specifically to ECs within tumors.
    Full-text · Article · Jun 2013 · PLoS ONE
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