北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学第二临床医学院  > 期刊论文
学科主题: 临床医学
题名:
Knockout of alpha A-Crystallin Inhibits Ocular Neovascularization
作者: Xu, Qiong1; Bai, Yujing1; Huang, Lvzhen1; Zhou, Peng2; Yu, Wenzhen1; Zhao, Mingwei1
关键词: alpha A-crystallin ; human umbilical vein endothelial cell ; neovascularization ; oxygen-induced retinopathy ; choroidal neovascularization ; vascular endothelial growth factor
刊名: INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
发表日期: 2015-02-01
DOI: 10.1167/iovs.14-14734
卷: 56, 期:2, 页:816-826
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Ophthalmology
研究领域[WOS]: Ophthalmology
关键词[WOS]: ENDOTHELIAL GROWTH-FACTOR ; MURINE CORNEAL NEOVASCULARIZATION ; OXYGEN-INDUCED RETINOPATHY ; ANTI-VEGF THERAPY ; B-CRYSTALLIN ; CHOROIDAL NEOVASCULARIZATION ; MACULAR DEGENERATION ; RETINAL NEOVASCULARIZATION ; SIGNALING PATHWAYS ; EYE DISEASE
英文摘要:

PURPOSE. The present study aimed to investigate the effects of alpha A-crystallin on pathologic ocular neovascularization.

METHODS. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro study, and alpha A-crystallin-knockout (CRYAA[-/-]) mice were used for the in vivo study. alpha A-crystallin was knocked down in HUVECs by using a specific small interfering RNA (siRNA), and the effects of aA-crystallin knockdown on proliferation, migration, tube formation, and apoptosis were evaluated. Enzyme-linked immunosorbent assays were performed to investigate extracellular concentrations of vascular endothelial growth factor (VEGF). In vivo mouse models of oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) were generated by using CRYAA(-/-) mice. The nonperfused area in the OIR model was measured in flat-mounted retinas, and angiogenesis resulting in CNV was evaluated in retinal sections. Western blot analysis was performed to investigate the phosphorylation status of vascular endothelial growth factor receptor 2 (VEGFR2, high affinity receptor for VEGF), AKT, PLC gamma 1, FAK, Src, p42/p44MAPK, p38MAPK, caspase-3, and caspase-9 in cultured HUVECs, as well as in the OIR and CNV models.

RESULTS. The CRYAA siRNA not only induced HUVEC apoptosis but also inhibited exogenous and endogenous VEGF-induced cell activities, including proliferation, migration, and tube formation. Pathologic neovascularization was attenuated in the CRYAA(-/-) murine OIR and CNV models. Both in vitro and in vivo, the inhibition of angiogenesis was mediated by the suppression of VEGF secretion and the inhibition of the VEGFR2 signaling pathway; VEGFR2, AKT, PLC gamma 1, FAK, Src, p42/p44MAPK, and p38 MAPK all showed reduced phosphorylation levels. In addition, CRYAA knockout led to increased levels of cleaved caspase-9 and caspase-3.

CONCLUSIONS. Knockout of alpha A-crystallin inhibited pathologic neovascularization through the VEGF and VEGFR2 signaling pathways both in vitro and in vivo. These results suggest that alpha A-crystallin could be a novel pharmaceutical target for the prevention of ocular neovascularization.

语种: 英语
所属项目编号: 81470651 ; 800965 ; 2011CB510200
项目资助者: National Basic Research Program of China ; National Basic Research Program of China (973 Program)
WOS记录号: WOS:000352137300015
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/66953
Appears in Collections:北京大学第二临床医学院_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Peking Univ, Peoples Hosp, Beijing Key Lab Diag & Treatment Retinal & Choroi, Key Lab Vis Loss & Restorat,Minist Educ,Dept Opht, Beijing 100044, Peoples R China
2.Pkwy Hlth Inc, Shanghai, Peoples R China

Recommended Citation:
Xu, Qiong,Bai, Yujing,Huang, Lvzhen,et al. Knockout of alpha A-Crystallin Inhibits Ocular Neovascularization[J]. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE,2015,56(2):816-826.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Xu, Qiong]'s Articles
[Bai, Yujing]'s Articles
[Huang, Lvzhen]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Xu, Qiong]‘s Articles
[Bai, Yujing]‘s Articles
[Huang, Lvzhen]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit
所有评论 (0)
暂无评论
 
评注功能仅针对注册用户开放,请您登录
您对该条目有什么异议,请填写以下表单,管理员会尽快联系您。
内 容:
Email:  *
单位:
验证码:   刷新
您在IR的使用过程中有什么好的想法或者建议可以反馈给我们。
标 题:
 *
内 容:
Email:  *
验证码:   刷新

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace