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学科主题: 临床医学
题名:
The role of SLIT-ROBO signaling in proliferative diabetic retinopathy and retinal pigment epithelial cells
作者: Zhou, Weiyan1; Yu, Wenzhen1; Xie, Wankun1; Huang, Lvzhen1; Xu, Yongsheng2; Li, Xiaoxin1
刊名: MOLECULAR VISION
发表日期: 2011-06-08
卷: 17, 期:170-71, 页:1526-1536
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Ophthalmology
研究领域[WOS]: Biochemistry & Molecular Biology ; Ophthalmology
关键词[WOS]: ENDOTHELIAL-CELLS ; GROWTH-FACTORS ; RPE CELLS ; RECEPTORS ; MIGRATION ; GUIDANCE ; VITREORETINOPATHY ; COMPLICATIONS ; ANGIOGENESIS ; MEMBRANES
英文摘要:

Purpose: SLIT-ROBO signaling acts as a cue in neuronal guidance and plays a role in vasculogenesis and angiogenesis. The aim of this study is to explore the effects of robo1 and slit2 on the formation of fibrovascular membranes (FVMs) in samples from patients with proliferative diabetic retinopathy. The effects of advanced glycation end products (AGEs) on robo1 and slit2 expression in human retinal pigment epithelium (RPE) cells and the role of recombinant N-SLIT2 protein in human RPE cell regulation were investigated.

Methods: Immunohistochemistry was performed to determine the presence and distribution of robo1 and slit2 in FVMs, and to confirm the effects of SLIT-ROBO signaling on FVM formation. The expression levels of robo1 and slit2 in RPE cells under basal and differential concentrations of AGEs were measured using real-time reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting, or enzyme-linked immunosorbent assay. LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), was used to help determine the AGE signaling mechanism. Recombinant N-SLIT2 protein was used to study the effects of slit2 on RPE cells in vitro. Cell proliferation, migration, and cell cycling were assessed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay assay (MTT) assay, a Boyden chamber assay, and flow cytometry. Real-time RT-PCR and enzyme-linked immunosorbent assay were used to study vascular endothelial growth factor (VEGF) mRNA expression in and VEGF protein secretion from RPE cells.

Results: Robo1 and Slit2 were expressed in FVMs in RPE cells coimmunostained for pancytokeratin. AGEs resulted in an increase in robo1 and slit2 levels in RPE cells, and inhibition of PI3K-blocked robo1 and slit2 expression. Recombinant N-SLIT2 protein increased proliferation, attachment, and migration of the RPE cells, and these cells demonstrated significant accumulation in the S phase compared to control cells. Furthermore, RPE cells treated with exogenous N-SLIT2 protein had higher levels of VEGF mRNA expression and VEGF protein secretion (p<0.05).

Conclusions: Robo1 and slit2 may play a role in the formation of FVMs. The presence of AGEs increased levels of robo1 and slit2 in human RPE cells via signaling through the PI3K/Akt pathway. Recombinant N-SLIT2 protein increased the biologic activity of RPE cells, as well as the expression of VEGF. From these results, we may conclude that SLIT-ROBO signaling potentially contributes to the development of diabetic retinopathy.

语种: 英语
所属项目编号: RDB2009-44 ; 2011CB510200
项目资助者: Peking University People&prime ; s Hospital ; National Basic Research Program of China (973 Program)
WOS记录号: WOS:000291442100002
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67346
Appears in Collections:北京大学第二临床医学院_期刊论文

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作者单位: 1.Peking Univ, Peoples Hosp, Key Lab Vis Loss & Restorat, Dept Ophthalmol,Minist Educ, Beijing 100044, Peoples R China
2.Peking Univ, Hosp 3, Clin Stem Cell Ctr, Beijing 100044, Peoples R China

Recommended Citation:
Zhou, Weiyan,Yu, Wenzhen,Xie, Wankun,et al. The role of SLIT-ROBO signaling in proliferative diabetic retinopathy and retinal pigment epithelial cells[J]. MOLECULAR VISION,2011,17(170-71):1526-1536.
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