Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization
Knockout of insulin and IGF-1 receptors on vascular endothelial cells protects against retinal neovascularization
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DOI：
10.1172/jci200317455
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发表时间：
2003-06-01
影响因子：
15.9
通讯作者：
Kahn, CR
中科院分区：
文献类型：
--
作者：
Kondo, T;Vicent, D;Kahn, CR
胰岛素和IGF-1都与视网膜内皮细胞生长、新生血管形成和糖尿病视网膜病变的控制有关。为了精确定义胰岛素和IGF-1信号在内皮细胞中的作用，我们使用氧诱导的视网膜病变模型来研究血管内皮细胞特异性敲除胰岛素受体（VENIRKO）或IGF-1受体（VENIFARKO）的小鼠。在相对缺氧后，与对照组相比，VENIRKO小鼠显示视网膜新生血管减少57%。这与VEGF、eNOS和内皮素-1的钝性升高有关。相比之下，VENIFARKO小鼠仅显示出34%的新血管形成减少和非常适度的介质产生减少。这些数据表明，胰岛素和胰岛素样生长因子-1信号在内皮细胞中发挥作用，通过表达血管介质的视网膜新生血管，胰岛素的作用是最重要的在这个过程中。
Both insulin and IGF-1 have been implicated in control of retinal endothelial cell growth, neovascularization, and diabetic retinopathy. To precisely define the role of insulin and IGF-1 signaling in endothelium in these processes, we have used the oxygen-induced retinopathy model to study mice with a vascular endothelial cell-specific knockout of the insulin receptor (VENIRKO) or IGF-1 receptor (VENIFARKO). Following relative hypoxia, VENIRKO mice show a 57% decrease in retinal neovascularization as compared with controls. This is associated with a blunted rise in VEGF, eNOS, and endothelin-1. By contrast, VENIFARKO mice show only a 34% reduction in neovascularization and a very modest reduction in mediator generation. These data indicate that both insulin and IGF-1 signaling in endothelium play a role in retinal neovascularization through the expression of vascular mediators, with the effect of insulin being most important in this process.