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.
Keywords: Angiogenesis; Bioinformatics analysis; Diabetic retinopathy.