Purinergic P2Y2 receptors modulate endothelial sprouting

被引：0

作者：

Severin Mühleder

Christiane Fuchs

José Basílio

Dorota Szwarc

Karoline Pill

Krystyna Labuda

Paul Slezak

Christian Siehs

Johannes Pröll

Eleni Priglinger

Carsten Hoffmann

Wolfgang G. Junger

Heinz Redl

Wolfgang Holnthoner

机构：

[1] AUVA Research Center,Ludwig Boltzmann Institute for Experimental and Clinical Traumatology

[2] Austrian Cluster for Tissue Regeneration,Department Life Science Engineering

[3] Kompetenzzentrum für MechanoBiologie (INTERREG V-A AT-CZ ATCZ133),Department of Vascular Biology and Thrombosis Research

[4] University of Applied Sciences Technikum Wien,Center for Medical Research

[5] Medical University of Vienna,Institut für Molekulare Zellbiologie, CMB

[6] Mag. Dipl.-Ing. Dr. Christian Siehs,Center for Molecular Biomedicine

[7] IT-Services,Department of Surgery

[8] GLN 9110002040261,Wellman Center for Photomedicine

[9] Johannes Kepler University,undefined

[10] Universitätsklinikum Jena,undefined

[11] Friedrich-Schiller-Universität,undefined

[12] Beth Israel Deaconess Medical Center,undefined

[13] Harvard Medical School,undefined

[14] Massachusetts General Hospital,undefined

[15] Red Cross Blood Transfusion Service,undefined

来源：

Cellular and Molecular Life Sciences | 2020年 / 77卷

关键词：

Endothelial; Purinergic; Angiogenesis; P2Y; Tip cell; Sprouting;

D O I：

暂无

中图分类号：

学科分类号：

摘要：

Purinergic P2 receptors are critical regulators of several functions within the vascular system, including platelet aggregation, vascular inflammation, and vascular tone. However, a role for ATP release and P2Y receptor signalling in angiogenesis remains poorly defined. Here, we demonstrate that blood vessel growth is controlled by P2Y2 receptors. Endothelial sprouting and vascular tube formation were significantly dependent on P2Y2 expression and inhibition of P2Y2 using a selective antagonist blocked microvascular network generation. Mechanistically, overexpression of P2Y2 in endothelial cells induced the expression of the proangiogenic molecules CXCR4, CD34, and angiopoietin-2, while expression of VEGFR-2 was decreased. Interestingly, elevated P2Y2 expression caused constitutive phosphorylation of ERK1/2 and VEGFR-2. However, stimulation of cells with the P2Y2 agonist UTP did not influence sprouting unless P2Y2 was constitutively expressed. Finally, inhibition of VEGFR-2 impaired spontaneous vascular network formation induced by P2Y2 overexpression. Our data suggest that P2Y2 receptors have an essential function in angiogenesis, and that P2Y2 receptors present a therapeutic target to regulate blood vessel growth.

引用

页码：885 / 901

页数：16

共 146 条

[1] Burnstock G(2014)Purinergic signaling and blood vessels in health and disease Pharmacol Rev 66 102-192
[2] Ralevic V(2012)Purinergic signaling during inflammation N Engl J Med 367 2322-2333
[3] Eltzschig HK(2002)P2 receptor expression profiles in human vascular smooth muscle and endothelial cells J Cardiovasc Pharmacol 40 841-853
[4] Sitkovsky MV(2014)P2Y2 R activation by nucleotides promotes skin wound-healing process Exp Dermatol 23 480-485
[5] Robson SC(2015)Extracellular uridine triphosphate and adenosine triphosphate attenuate endothelial inflammation through miR-22-mediated ICAM-1 inhibition J Vasc Res 52 71-80
[6] Wang L(2009)Purinergic regulation of vascular endothelial growth factor signaling in angiogenesis Br J Cancer 100 1465-1470
[7] Karlsson L(2009)Development of selective agonists and antagonists of P2Y receptors Purinergic Signal 5 75-89
[8] Moses S(2004)The P2Y2 nucleotide receptor mediates vascular cell adhesion molecule-1 expression through interaction with VEGF receptor-2 (KDR/Flk-1) J Biol Chem 279 35679-35686
[9] Jin H(2014)The P2Y2 receptor interacts with VE-cadherin and VEGF receptor-2 to regulate Rac1 activity in endothelial cells J Biomed Sci Eng 7 1105-1121
[10] Seo J(2016)P2Y2 nucleotide receptor mediates arteriogenesis in a murine model of hind limb ischemia J Vasc Surg 63 216-225

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