VEGFR1 signaling in retinal angiogenesis and microinflammation.
VEGFR1 signaling in retinal angiogenesis and microinflammation.
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视网膜血管生成和微炎症中的VEGFR1信号传导。
DOI：
10.1016/j.preteyeres.2021.100954
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发表时间：
2021-09
影响因子：
17.8
通讯作者：
Langmann T
中科院分区：
文献类型：
--
作者：
Uemura A;Fruttiger M;D'Amore PA;De Falco S;Joussen AM;Sennlaub F;Brunck LR;Johnson KT;Lambrou GN;Rittenhouse KD;Langmann T
血管内皮生长因子受体(VEGFR)五种配体(血管内皮生长因子-A、-B、-C、-D和胎盘生长因子[PlGF])组成了血管内皮生长因子家族。血管内皮生长因子-A与血管内皮生长因子受体1和2(VEGFR1/2)结合，而血管内皮生长因子-B和血小板生长因子仅与血管内皮生长因子受体1结合。虽然已经对VEGFR2进行了大量的研究，以阐明其在视网膜疾病中的关键作用，但最近的研究表明，VEGFR1及其配体家族在视网膜内的血管生成、血管通透性和微炎症级联中的重要性和参与。VEGFR1的表达依赖于微环境，在缺氧和炎症条件下有不同的调节，已在视网膜和脉络膜内皮细胞、周细胞、视网膜和脉络膜单核吞噬细胞(包括小胶质细胞)、Müler细胞、光感受器细胞和视网膜色素上皮中检测到。虽然VEGFR1的VEGF-A诱骗功能已经确立，但其直接信号的后果还不是很清楚。VEGFR1活化可影响血管通透性，诱导巨噬细胞和小胶质细胞产生促炎和促血管生成介质。然而，VEGFR1配体(VEGF-A、PlGF和VEGF-B)相互竞争受体结合和异源二聚体的能力，使我们无法理解VEGFR1信号在糖尿病视网膜病变、视网膜血管阻塞、早产儿视网膜病变和年龄相关性黄斑变性中的相对作用。在临床上，抗血管内皮生长因子药物已经被证明在这些病理过程中具有转化作用，它们对血管内皮生长因子受体信号转导的影响仍然是一个充满机会的领域，有待进一步研究。
Five vascular endothelial growth factor receptor (VEGFR) ligands (VEGF-A, -B, –C, -D, and placental growth factor [PlGF]) constitute the VEGF family. VEGF-A binds VEGF receptors 1 and 2 (VEGFR1/2), whereas VEGF-B and PlGF only bind VEGFR1. Although much research has been conducted on VEGFR2 to elucidate its key role in retinal diseases, recent efforts have shown the importance and involvement of VEGFR1 and its family of ligands in angiogenesis, vascular permeability, and microinflammatory cascades within the retina. Expression of VEGFR1 depends on the microenvironment, is differentially regulated under hypoxic and inflammatory conditions, and it has been detected in retinal and choroidal endothelial cells, pericytes, retinal and choroidal mononuclear phagocytes (including microglia), Müller cells, photoreceptor cells, and the retinal pigment epithelium. Whilst the VEGF-A decoy function of VEGFR1 is well established, consequences of its direct signaling are less clear. VEGFR1 activation can affect vascular permeability and induce macrophage and microglia production of proinflammatory and proangiogenic mediators. However the ability of the VEGFR1 ligands (VEGF-A, PlGF, and VEGF-B) to compete against each other for receptor binding and to heterodimerize complicates our understanding of the relative contribution of VEGFR1 signaling alone toward the pathologic processes seen in diabetic retinopathy, retinal vascular occlusions, retinopathy of prematurity, and age-related macular degeneration. Clinically, anti-VEGF drugs have proven transformational in these pathologies and their impact on modulation of VEGFR1 signaling is still an opportunity-rich field for further research.
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影响因子：
16.6
作者：
Aspalter IM;Gordon E;Dubrac A;Ragab A;Narloch J;Vizán P;Geudens I;Collins RT;Franco CA;Abrahams CL;Thurston G;Fruttiger M;Rosewell I;Eichmann A;Gerhardt H
通讯作者：
Gerhardt H
影响因子：
13.7
作者：
Bhandari, Sanjeeb;Nguyen, Vuong;Barthelmes, Daniel
通讯作者：
Barthelmes, Daniel
影响因子：
82.9
作者：
Autiero, M;Waltenberger, J;Carmeliet, P
通讯作者：
Carmeliet, P
影响因子：
4.3
作者：
Bentley K;Mariggi G;Gerhardt H;Bates PA
通讯作者：
Bates PA
DOI：
10.1073/pnas.95.2.548
发表时间：
1998-01-20
影响因子：
11.1
作者：
Achen, MG;Jeltsch, M;Stacker, SA
通讯作者：
Stacker, SA