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糖尿病大鼠视网膜基因功能与表达的生物信息学分析

Bioinformatic analysis of retinal gene function and expression in diabetic rats.

作者信息

Zhao Wenjuan, Wang Dong, Zhao Jun, Zhao Wenqing

机构信息

Department of Ophthalmology, Shandong University Affiliated Jinan Central Hospital, Jinan, Shandong 250013, P.R. China.

School of Management Science and Engineering, Shandong University of Finance and Economics, Jinan, Shandong 250014, P.R. China.

出版信息

Exp Ther Med. 2017 Sep;14(3):2485-2492. doi: 10.3892/etm.2017.4805. Epub 2017 Jul 19.

Abstract

The aim of the present study was to investigate the changes in retinal gene expression at three time points and assess the underlying molecular mechanisms of diabetic retinopathy (DR) in a streptozotocin (STZ)-induced diabetes rat model using bioinformatics analysis. The gene expression profile of GSE28831 was extracted from the Gene Expression Omnibus database and differentially expressed genes (DEGs) were identified at three different time points (1, 4 and 12 weeks) using the limma package in R language. Gene ontology (GO) enrichment analysis of DEGs was performed followed by a principal component and pathway enrichment analysis of the selected DEGs along with protein-protein interaction network construction at the three time points. A total of 402, 105 and 213 DEGs were screened at 1, 4 and 12 weeks, respectively. In addition, the expression of 8 genes was identified to be significantly different at different time points, including cytochrome P450 2B2 (CYP2B2; downregulated gene; P=0.048; at 1 week), mannan binding lectin-associated serine protease-2 (MASP2; downregulated gene; P=0.044), lecithin retinol acyltransferase (LRAT; downregulated gene; P=0.015), retinal pigment epithelium (RPE)-specific protein 65 kDa (RPE65; downregulated gene; P=0.025), 11-cis-retinoldehydrogenase (RDH5; downregulated gene; P=0.04; at 4 weeks), mitogen-activated protein kinase 13 (MAPK13; upregulated gene; P=0.036), LRAT (downregulated gene; P=0.01) and RPE65 (downregulated gene; P=0.009; at 12 weeks). Furthermore, pathway enrichment and GO enrichment analyses revealed that DEGs at 4 weeks were primarily enriched in retinol metabolism and processes associated with visual functions, including 'visual perception' and 'retinol metabolism'. DEGs, including CYP2B2, MASP2, LRAT, RPE65, RDH5 and MAPK13 may be potential targets for the diagnosis and treatment of DR. Thus, the current study demonstrated that abnormal visual functions occur at 4 weeks in STZ-induced diabetic rats. This may provide a scientific basis for the diagnosis and treatment of DR because DEGs may be used to facilitate the development of novel therapeutic strategies to diagnose and treat DR.

摘要

本研究的目的是在链脲佐菌素(STZ)诱导的糖尿病大鼠模型中,通过生物信息学分析,研究三个时间点视网膜基因表达的变化,并评估糖尿病视网膜病变(DR)的潜在分子机制。从基因表达综合数据库中提取GSE28831的基因表达谱,并使用R语言中的limma软件包在三个不同时间点(1、4和12周)鉴定差异表达基因(DEG)。对DEG进行基因本体(GO)富集分析,随后对选定的DEG进行主成分和通路富集分析,并在三个时间点构建蛋白质-蛋白质相互作用网络。在1、4和12周时分别筛选出402、105和213个DEG。此外,鉴定出8个基因在不同时间点的表达有显著差异,包括细胞色素P450 2B2(CYP2B2;下调基因;P = 0.048;在1周时)、甘露聚糖结合凝集素相关丝氨酸蛋白酶-2(MASP2;下调基因;P = 0.044)、卵磷脂视黄醇酰基转移酶(LRAT;下调基因;P = 0.015)、视网膜色素上皮(RPE)特异性65 kDa蛋白(RPE65;下调基因;P = 0.025)、11-顺式视黄醇脱氢酶(RDH5;下调基因;P = 0.04;在4周时)、丝裂原活化蛋白激酶13(MAPK13;上调基因;P = 0.036)、LRAT(下调基因;P = 0.01)和RPE65(下调基因;P = 0.009;在12周时)。此外,通路富集和GO富集分析表明,4周时的DEG主要富集在视黄醇代谢以及与视觉功能相关的过程中,包括“视觉感知”和“视黄醇代谢”。包括CYP2B2、MASP2、LRAT、RPE65、RDH5和MAPK13在内的DEG可能是DR诊断和治疗的潜在靶点。因此,本研究表明,STZ诱导的糖尿病大鼠在4周时出现视觉功能异常。这可能为DR的诊断和治疗提供科学依据,因为DEG可用于促进开发诊断和治疗DR的新型治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6eec/5609221/6202c0b22f55/etm-14-03-2485-g00.jpg

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