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学科主题: 临床医学
题名:
Targeting of integrin-linked kinase with a small interfering RNA suppresses progression of experimental proliferative vitreoretinopathy
作者: 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
发表日期: 2008-12-01
DOI: 10.1016/j.exer.2008.09.008
卷: 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
所属项目编号: 2005CB724307
项目资助者: National Basic Research Program of China
WOS记录号: WOS:000261823900009
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/64205
Appears in Collections:北京大学第二临床医学院_眼科_期刊论文

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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

Recommended Citation:
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.
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