Blockade of vascular endothelial growth factor receptor 1 prevents inflammation and vascular leakage in diabetic retinopathy.
Blockade of vascular endothelial growth factor receptor 1 prevents inflammation and vascular leakage in diabetic retinopathy.
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DOI：
10.1155/2015/605946
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发表时间：
2015
影响因子：
1.9
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
He J;Wang H;Liu Y;Li W;Kim D;Huang H
糖尿病视网膜病变（DR）是工作年龄成年人失明的主要原因。本研究采用链脲佐菌素（STZ）或胰岛素2（Insulin 2）基因突变（秋田）诱导的糖尿病小鼠模型，观察血管内皮生长因子受体1（VEGFR 1）阻断对糖尿病视网膜病变（DR）并发症的影响。蛋白质表达和定位通过蛋白质印迹（WB）和免疫荧光（IF）检测。通过PCR阵列和实时PCR定量mRNA表达。VEGFR 1信号传导的活性被称为MF 1的中和抗体阻断。通过测量[3 H]-甘露醇示踪剂向视网膜的渗漏和白蛋白的IF染色来评价血管渗漏。VEGFR 1阻断显著抑制糖尿病相关的血管渗漏、白细胞-内皮细胞（EC）粘附（或视网膜白细胞停滞）、细胞间粘附分子-（ICAM-）1蛋白的表达、紧密连接蛋白封闭小带-（ZO-）1和细胞粘附蛋白血管内皮（VE）钙粘蛋白的异常定位和变性。此外，VEGFR 1阻断干扰了10种新的细胞因子和趋化因子的基因表达：cxcl 10、il 10、ccl 8、il 1f 6、cxcl 15、ccl 4、il 13、ccl 6、casp 1和ccr 5。这些结果表明，VEGFR 1介导DR并发症，靶向该信号通路代表了预防和治疗DR的潜在治疗策略。
Diabetic retinopathy (DR) is a leading cause of blindness in working age adults. The objective of this study is to investigate the effects of vascular endothelial growth factor receptor 1 (VEGFR1) blockade on the complications of DR. Experimental models of diabetes were induced with streptozotocin (STZ) treatment or Insulin2 gene mutation (Akita) in mice. Protein expression and localization were examined by western blots (WB) and immunofluorescence (IF). mRNA expression was quantified by PCR array and real-time PCR. The activity of VEGFR1 signaling was blocked by a neutralizing antibody called MF1. Vascular leakage was evaluated by measuring the leakage of [3H]-mannitol tracer into the retina and the IF staining of albumin. VEGFR1 blockade significantly inhibited diabetes-related vascular leakage, leukocytes-endothelial cell (EC) adhesion (or retinal leukostasis), expression of intercellular adhesion molecule- (ICAM-) 1 protein, abnormal localization and degeneration of the tight junction protein zonula occludens- (ZO-) 1, and the cell adhesion protein vascular endothelial (VE) cadherin. In addition, VEGFR1 blockade interfered with the gene expression of 10 new cytokines and chemokines: cxcl10, il10, ccl8, il1f6, cxcl15, ccl4, il13, ccl6, casp1, and ccr5. These results suggest that VEGFR1 mediates complications of DR and targeting this signaling pathway represents a potential therapeutic strategy for the prevention and treatment of DR.
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影响因子：
3.7
作者：
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