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Targeting of integrin-linked kinase with a small interfering RNA suppresses progression of experimental proliferative vitreoretinopathy
Guo, Lili1; Yu, Wenzhen1; Li, Xiaoxin1; Zhao, Gang2; Liang, Jianhong1; He, Peiying3; Wang, Kai1; Zhou, Peng1; Jiang, Yanrong1; Zhao, Mingwei1
关键词human retinal pigment epithelial cell integrin-linked kinase small interfering RNA proliferative vitreoretinopathy
刊名EXPERIMENTAL EYE RESEARCH
2008-12-01
DOI10.1016/j.exer.2008.09.008
87期:6页:551-560
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]MASSIVE PERIRETINAL PROLIFERATION ; PROTEIN-KINASE ; RETINAL-DETACHMENT ; PIGMENT EPITHELIUM ; EXPERIMENTAL-MODEL ; CELL-MIGRATION ; CANCER CELLS ; INHIBITION ; SURVIVAL ; ILK
英文摘要

Integrin-linked kinase (ILK) is a serine/threonine kinase that interacts through its COOH terminus with beta 1 and beta 3 integrins, which mediates a diversity of cell functions by coupling integrins and growth factors to cascades of downstream signaling events, The purpose of this work was to investigate the effects of ILK on development of experimental proliferative vitreoretinopathy (PVR). Cultured human RPE cell line D407 was knocked down for ILK using a small interfering RNA (siRNA). For this, cellular ILK expression was quantified by real-time quantitative PCR, Western blot analysis and immunocytochemical assay, and cytotoxicity of transfection was determined by MTT assay. Moreover, cell attachment, spreading, migration, microfilament dynamics, and cell cycling assays were performed. Furthermore, the impact of the ILK-specific siRNA on PVR was tested using a rabbit model in which PVR was induced by the injection of human RPE cells. Prevalence of PVR and retinal detachment were determined by indirect ophthalmoscopy on clays 1, 3, 7,14, 21 and 28 post-injection. The results showed that blocking the expression of ILK by siRNA significantly inhibited human RPE cell attachment, spreading, migration and proliferation. The knockdown of ILK also disturbed F-actin assembly and induced a cellular arrest in the G1 phase of the cell cycle. Though the eyes injected with ILK-specific siRNA also developed features of PVR, the severities of day 28 post-injection were significantly lower than those in the control eyes (P < 0.01). We conclude that targeting of ILK with a small interfering RNA not only inhibits human RPE cell attachment, spreading, migration and proliferation in vitro, but also effectively suppresses development of proliferative vitreoretinopathy in a rabbit model. This may be a potential therapeutic usefulness in treating PVR. (C) 2008 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000261823900009
项目编号2005CB724307
资助机构National Basic Research Program of China
引用统计
被引频次:14[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/64205
专题北京大学第二临床医学院_眼科
作者单位1.Peking Univ, Peoples Hosp, Dept Ophthalmol, Beijing 100044, Peoples R China
2.Beijing Hosp, Dept Gen Surg, Minist Health, Beijing 100730, Peoples R China
3.Peking Univ, Peoples Hosp, Ctr Lab, Beijing 100044, Peoples R China
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GB/T 7714
Guo, Lili,Yu, Wenzhen,Li, Xiaoxin,et al. Targeting of integrin-linked kinase with a small interfering RNA suppresses progression of experimental proliferative vitreoretinopathy[J]. EXPERIMENTAL EYE RESEARCH,2008,87(6):551-560.
APA Guo, Lili.,Yu, Wenzhen.,Li, Xiaoxin.,Zhao, Gang.,Liang, Jianhong.,...&Zhao, Mingwei.(2008).Targeting of integrin-linked kinase with a small interfering RNA suppresses progression of experimental proliferative vitreoretinopathy.EXPERIMENTAL EYE RESEARCH,87(6),551-560.
MLA Guo, Lili,et al."Targeting of integrin-linked kinase with a small interfering RNA suppresses progression of experimental proliferative vitreoretinopathy".EXPERIMENTAL EYE RESEARCH 87.6(2008):551-560.
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