全面分析早期糖尿病视网膜病变中的血管生成相关基因和通路。
Comprehensive analysis of angiogenesis-related genes and pathways in early diabetic retinopathy.
机构信息
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
National Clinical Research Center for Eye Diseases, Shanghai Key Laboratory of Ocular Fundus Diseases; Shanghai Engineering Center for Visual Science and Photomedicine; Shanghai engineering center for precise diagnosis and treatment of eye diseases, Shanghai, P.R. China.
出版信息
BMC Med Genomics. 2020 Sep 29;13(1):142. doi: 10.1186/s12920-020-00799-6.
BACKGROUND
Angiogenesis is an important parameter in the development of diabetic retinopathy (DR), and it is indicative of an early stage evolving into a late phase. Therefore, examining the role of angiogenic factors in early DR is crucial to understanding the mechanism of neovascularization.
METHODS
The present study identified hub genes and pathways associated with angiogenesis in early DR using bioinformatics analysis. Genes from published literature and Gene Expression Omnibus (GEO) were collected and analysed.
RESULTS
We collected 73 genes from 70 published studies in PubMed, which were referred to as DR-related gene set 1 (DRgset1). The gene expression profile of GSE12610 was downloaded, and 578 differentially expressed genes (DEGs) between diabetic and normal samples were identified. DEGs and DRgset1 were further combined to create DR-related gene set 2 (DRgset2). After an enrichment analysis, we identified 12 GO terms and 2 pathways associated with neovascularization in DRgset1, and 8 GO terms and 2 pathways in DRgset2. We found 39 new genes associated with angiogenesis and verified 8 candidate angiogenesis-related genes in DR cells using real-time PCR: PIK3CB, ALDH3A1, ITGA7, FGF23, THBS1, COL1A1, MAPK13, and AIF1. We identified 10 hub genes associated with neovascularization by constructing a protein-protein interaction (PPI) network: TNF, VEGFA, PIK3CB, TGFB1, EDN1, MMP9, TLR4, PDGFB, MMP2, and THBS1.
CONCLUSIONS
The present study analysed angiogenesis-related genes and pathways in early DR in a comprehensive and systematic manner. PIK3CB, ALDH3A1, ITGA7, FGF23, THBS1, COL1A1, MAPK13, and AIF1 may be the candidate genes to further explore the mechanisms of angiogenesis in early DR. TNF, PIK3CB, TGFB1, EDN1, MMP9, TLR4, PDGFB, MMP2, and THBS1 may be new targets for early neovascularization therapy in the future.
背景
血管生成是糖尿病视网膜病变（DR）发展的一个重要参数，它预示着疾病从早期阶段向晚期阶段的演变。因此，研究血管生成因子在早期 DR 中的作用对于理解新生血管化的机制至关重要。
方法
本研究通过生物信息学分析，确定了早期 DR 中与血管生成相关的枢纽基因和途径。从已发表的文献和基因表达综合数据库（GEO）中收集基因进行分析。
结果
我们从 PubMed 中 70 项已发表的研究中收集了 73 个基因，称为 DR 相关基因集 1（DRgset1）。下载 GSE12610 的基因表达谱，鉴定出糖尿病样本和正常样本之间的 578 个差异表达基因（DEGs）。将 DEGs 和 DRgset1 进一步组合，创建了 DR 相关基因集 2（DRgset2）。经过富集分析，我们在 DRgset1 中发现了与 DR 中新生血管化相关的 12 个 GO 术语和 2 个途径，在 DRgset2 中发现了 8 个 GO 术语和 2 个途径。我们发现了 39 个与血管生成相关的新基因，并通过实时 PCR 验证了 DR 细胞中 8 个候选血管生成相关基因：PIK3CB、ALDH3A1、ITGA7、FGF23、THBS1、COL1A1、MAPK13 和 AIF1。通过构建蛋白质-蛋白质相互作用（PPI）网络，我们鉴定出 10 个与新生血管化相关的枢纽基因：TNF、VEGFA、PIK3CB、TGFB1、EDN1、MMP9、TLR4、PDGFB、MMP2 和 THBS1。
结论
本研究全面系统地分析了早期 DR 中与血管生成相关的基因和途径。PIK3CB、ALDH3A1、ITGA7、FGF23、THBS1、COL1A1、MAPK13 和 AIF1 可能是进一步探索早期 DR 中血管生成机制的候选基因。TNF、PIK3CB、TGFB1、EDN1、MMP9、TLR4、PDGFB、MMP2 和 THBS1 可能是未来早期新生血管化治疗的新靶点。
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