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基于微阵列的急性原发性闭角型青光眼患者外周血基因表达谱分析

Microarray-based analysis of gene expression profiles in peripheral blood of patients with acute primary angle closure.

作者信息

Jeoung Jin Wook, Ko Jung Hwa, Kim Yu Jeong, Kim Yong Woo, Park Ki Ho, Oh Joo Youn

机构信息

a Department of Ophthalmology , Seoul National University Hospital , Seoul , South Korea.

b Laboratory of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center , Seoul National University Hospital Biomedical Research Institute , Seoul , South Korea.

出版信息

Ophthalmic Genet. 2017 Dec;38(6):520-526. doi: 10.1080/13816810.2017.1300922. Epub 2017 Mar 21.

DOI:10.1080/13816810.2017.1300922
PMID:28323501
Abstract

BACKGROUND

We investigated the expression of molecules in peripheral blood mononuclear cells (PBMCs) and plasma of patients with acute primary angle closure (APAC).

MATERIALS AND METHODS

Peripheral blood was collected from patients with APAC (n = 10) and age-matched controls (n = 5). The gene transcription profile was analyzed in PBMCs using microarrays and validated by real-time reverse transcription polymerase chain reaction (RT-PCR). The levels of secreted proteins were evaluated in plasma by ELISA.

RESULTS

347 gene transcripts were up-regulated by 2-fold or more, and 696 transcripts down-regulated 2-fold or more in PBMCs from patients compared to controls. The most highly up-regulated gene was thrombospondin-1 (TSP-1, 8.66-fold increase), and the most down-regulated gene was prostaglandin-endoperoxide synthase 2 (PTGS2, 9.09-fold decrease). Real-time RT-PCR assay confirmed the increase of TSP-1 and the decrease of PTGS2 in PBMCs of patients. ELISA revealed that the levels of TSP-1 and active transforming growth factor (TGF)-β1 that is activated by TSP-1 were elevated in plasma of patients, while the level of prostaglandin E2 (PGE2) that is converted by PTGS2 was reduced. The plasma level of TSP-1 was positively correlated with that of active TGF-β1.

CONCLUSIONS

Our data suggest that the molecular network including TSP-1, TGF-β1, and PGE2 might be involved in the pathogenesis of APAC and PACG.

摘要

背景

我们研究了急性原发性闭角型青光眼(APAC)患者外周血单个核细胞(PBMCs)和血浆中分子的表达情况。

材料与方法

采集APAC患者(n = 10)和年龄匹配的对照组(n = 5)的外周血。使用微阵列分析PBMCs中的基因转录谱,并通过实时逆转录聚合酶链反应(RT-PCR)进行验证。通过酶联免疫吸附测定(ELISA)评估血浆中分泌蛋白的水平。

结果

与对照组相比,患者PBMCs中347个基因转录本上调2倍或更多,696个转录本下调2倍或更多。上调最显著的基因是血小板反应蛋白-1(TSP-1,增加8.66倍),下调最显著的基因是前列腺素内过氧化物合酶2(PTGS2,降低9.09倍)。实时RT-PCR检测证实患者PBMCs中TSP-1增加,PTGS2减少。ELISA显示患者血浆中TSP-1和由TSP-1激活的活性转化生长因子(TGF)-β1水平升高,而由PTGS2转化的前列腺素E2(PGE2)水平降低。血浆中TSP-1水平与活性TGF-β1水平呈正相关。

结论

我们的数据表明,包括TSP-1、TGF-β1和PGE2的分子网络可能参与了APAC和原发性闭角型青光眼(PACG)的发病机制。

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