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Blockade of vascular endothelial growth factor receptor 1 prevents inflammation and vascular leakage in diabetic retinopathy.

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WOS被引频次:28
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成果类型:
期刊论文
作者:
He, Jianbo;Wang, Hong;Liu, Ying;Li, Wen;Kim, Dorothy;Huang, Hu*
通讯作者:
Huang, Hu
作者机构:
[He, Jianbo] Guangxi Tumor Hosp & Inst, Nanning 530021, Guangxi, Peoples R China.
[Wang, Hong] Shandong Univ, Prov Hosp, Dept Ophthalmol, Jinan 250021, Shandong, Peoples R China.
[Liu, Ying; Li, Wen] Changsha Aier Eye Hosp, Changsha 410015, Hunan, Peoples R China.
[Liu, Ying; Li, Wen] Cent S Univ, Aier Sch Ophthalmol, Changsha 410015, Hunan, Peoples R China.
[Liu, Ying; Huang, Hu; Kim, Dorothy; Li, Wen] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
通讯机构:
[Huang, Hu] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, M017 Robert H & Clarice Smith Bldg,400 N Broadway, Baltimore, MD 21287 USA.
语种:
英文
期刊:
Journal of ophthalmology
ISSN:
2090-004X
年:
2015
卷:
2015
页码:
605946
文献类别:
WOS:Article
所属学科:
ESI学科类别:临床医学;WOS学科类别:Medicine, Research & Experimental;Ophthalmology
入藏号:
基金类别:
Wilmer Pooled Professor Funds, Research to Prevent Blindness; Science and Technology Development Plan of Shandong Province [013GSF31804]; Janssen Research and Development; Brightfocus Foundation
机构署名:
本校为其他机构
院系归属:
爱尔眼科学院
摘要:
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 [(3)H]-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.
参考文献:
Aiello LP, 1997, DIABETES, V46, P1473, DOI 10.2337/diabetes.46.9.1473
Al-Shabrawey M, 2008, INVEST OPHTH VIS SCI, V49, P3239, DOI 10.1167/iovs.08-1755
Antonetti DA, 2012, NEW ENGL J MED, V366, P1227, DOI 10.1056/NEJMra1005073
Behl Y, 2009, DIABETES, V58, P917, DOI 10.2337/db08-0537
Chen Y, 2009, AM J PATHOL, V175, P2676, DOI 10.2353/ajpath.2009.080945

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