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. 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. 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. 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.

中文翻译：

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早期糖尿病视网膜病变血管生成相关基因及通路的综合分析


血管生成是糖尿病视网膜病变（DR）发展的重要参数，它预示着早期阶段发展到晚期阶段。因此，检查血管生成因子在早期 DR 中的作用对于理解新生血管形成机制至关重要。本研究利用生物信息学分析确定了早期 DR 中与血管生成相关的中枢基因和通路。收集并分析了已发表文献和基因表达综合 (GEO) 中的基因。我们从 PubMed 上发表的 70 篇研究中收集了 73 个基因，将其称为 DR 相关基因集 1 (DRgset1)。下载GSE12610的基因表达谱，并鉴定出糖尿病和正常样本之间的578个差异表达基因（DEG）。 DEGs 和 DRgset1 进一步组合以创建 DR 相关基因集 2 (DRgset2)。经过富集分析后，我们在 DRgset1 中确定了 12 个 GO 术语和 2 个与新生血管相关的通路，在 DRgset2 中确定了 8 个 GO 术语和 2 个通路。我们发现了 39 个与血管生成相关的新基因，并使用实时 PCR 在 DR 细胞中验证了 8 个候选血管生成相关基因：PIK3CB、ALDH3A1、ITGA7、FGF23、THBS1、COL1A1、MAPK13 和 AIF1。我们通过构建蛋白质-蛋白质相互作用 (PPI) 网络，鉴定了 10 个与新生血管形成相关的中心基因：TNF、VEGFA、PIK3CB、TGFB1、EDN1、MMP9、TLR4、PDGFB、MMP2 和 THBS1。本研究全面系统地分析了早期DR中血管生成相关基因和通路。 PIK3CB、ALDH3A1、ITGA7、FGF23、THBS1、COL1A1、MAPK13和AIF1可能是进一步探讨早期DR血管生成机制的候选基因。 TNF、PIK3CB、TGFB1、EDN1、MMP9、TLR4、PDGFB、MMP2、THBS1可能成为未来早期新生血管治疗的新靶点。