VEGFR1-mediated pericyte ablation links VEGF and PlGF to cancer-associated retinopathy
VEGFR1-mediated pericyte ablation links VEGF and PlGF to cancer-associated retinopathy
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DOI：
10.1073/pnas.0911661107
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发表时间：
2010-01-12
影响因子：
11.1
通讯作者：
Cao, Yihai
中科院分区：
文献类型：
--
作者：
Cao, Renhai;Xue, Yuan;Cao, Yihai
VEGF协调细胞再生的复杂调节以及内皮细胞和血管周围细胞之间的相互作用; VEGF信号传导系统的功能障碍导致视网膜病变。在这里，我们表明，通过蛋白质植入、肿瘤和腺病毒载体全身递送VEGF和胎盘生长因子（PlGF）通过VEGF受体1（VEGFR 1）介导的信号通路从成熟的视网膜血管系统消融周细胞，导致血管渗漏增加。相反，我们证明VEGF受体2（VEGFR 2）主要在非血管光感受器和神经节细胞中表达。此外，VEGFR 1而不是VEGFR 2的阻断显著恢复成熟视网膜血管中的周细胞饱和度。我们的研究结果将VEGF和PlGF与癌症相关的视网膜病变联系起来，揭示了VEGFR 1配体介导的视网膜病变的分子机制，并将VEGFR 1定义为治疗视网膜病变的抗血管生成治疗的重要靶点。
VEGF coordinates complex regulation of cellular regeneration and interactions between endothelial and perivascular cells; dysfunction of the VEGF signaling system leads to retinopathy. Here, we show that systemic delivery of VEGF and placental growth factor (PlGF) by protein implantation, tumors, and adenoviral vectors ablates pericytes from the mature retinal vasculature through the VEGF receptor 1 (VEGFR1)-mediated signaling pathway, leading to increased vascular leakage. In contrast, we demonstrate VEGF receptor 2 (VEGFR2) is primarily expressed in nonvascular photo-receptors and ganglion cells. Moreover, blockade of VEGFR1 but not VEGFR2 significantly restores pericyte saturation in mature retinal vessels. Our findings link VEGF and PlGF to cancer-associated retinopathy, reveal the molecular mechanisms of VEGFR1 ligand-mediated retinopathy, and define VEGFR1 as an important target of antiangiogenic therapy for treatment of retinopathy.