Secretogranin III as a disease-associated ligand for antiangiogenic therapy of diabetic retinopathy.
Secretogranin III as a disease-associated ligand for antiangiogenic therapy of diabetic retinopathy.
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DOI：
10.1084/jem.20161802
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发表时间：
2017-04-03
期刊：
影响因子：
--
通讯作者：
Li W
中科院分区：
文献类型：
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作者：
LeBlanc ME;Wang W;Chen X;Caberoy NB;Guo F;Shen C;Ji Y;Tian H;Wang H;Chen R;Li W
LeBlanc等人利用比较配体组学发现secretogranin III （Scg3）是一种独特的与疾病相关的血管通透性和血管生成因子。scg3中和抗体对糖尿病视网膜病变小鼠血管渗漏和氧致视网膜病变小鼠视网膜新生有较好的缓解作用。糖尿病性视网膜病变（DR）是视网膜血管渗漏和/或新生血管形成导致视力丧失的主要原因。目前针对血管内皮生长因子（VEGF）的抗血管生成治疗效果有限。在这项研究中，我们将一种新的比较配体组学技术应用于糖尿病小鼠和正常小鼠，用于疾病相关内皮配体的差异定位。Secretogranin III （Scg3）是一种新的疾病相关配体，在糖尿病血管中具有选择性结合和血管生成活性，但在健康血管中没有。相反，VEGF与糖尿病和正常血管结合并诱导血管生成。Scg3和VEGF信号通过不同的受体通路。重要的是，scg3中和抗体能高效缓解糖尿病小鼠视网膜血管渗漏。此外，抗scg3还能阻止氧诱导视网膜病变小鼠（早产儿视网膜病变的替代模型）视网膜新生血管的形成。ROP是儿童视力受损的最常见原因，目前尚无批准的药物治疗。这些结果表明，Scg3是一种新的抗血管生成治疗DR和ROP的有希望的靶点。
LeBlanc et al. uncover secretogranin III (Scg3) as a unique disease-associated vascular permeability and angiogenic factor using comparative ligandomics. Scg3-neutralizing antibodies alleviate vascular leakage in diabetic retinopathy mice and retinal neovascularization in oxygen-induced retinopathy mice with high efficacy. Diabetic retinopathy (DR) is a leading cause of vision loss with retinal vascular leakage and/or neovascularization. Current antiangiogenic therapy against vascular endothelial growth factor (VEGF) has limited efficacy. In this study, we applied a new technology of comparative ligandomics to diabetic and control mice for the differential mapping of disease-related endothelial ligands. Secretogranin III (Scg3) was discovered as a novel disease-associated ligand with selective binding and angiogenic activity in diabetic but not healthy vessels. In contrast, VEGF bound to and induced angiogenesis in both diabetic and normal vasculature. Scg3 and VEGF signal through distinct receptor pathways. Importantly, Scg3-neutralizing antibodies alleviated retinal vascular leakage in diabetic mice with high efficacy. Furthermore, anti-Scg3 prevented retinal neovascularization in oxygen-induced retinopathy mice, a surrogate model for retinopathy of prematurity (ROP). ROP is the most common cause of vision impairment in children, with no approved drug therapy. These results suggest that Scg3 is a promising target for novel antiangiogenic therapy of DR and ROP.