Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Road, Nanjing, 211100, China.
Department of Healthcare management, Sir Run Run Hospital, Nanjing Medical University, 109 Longmian Road, Nanjing, 211100, China.
BMC Genom Data. 2022 Jul 7;23(1):52. doi: 10.1186/s12863-022-01047-9.
The application of cell-specific construction of transcription regulatory networks (TRNs) to identify their master regulators (MRs) in EMP2 induced vascular proliferation disorders has been largely unexplored.
Different expression gene (DEGs) analyses was processed with DESeq2 R package, for public RNA-seq transcriptome data of EMP2-treated hRPECs versus vector control (VC) or wild type (WT) hRPECs. Virtual Inference of protein activity by Enriched Regulon analysis (VIPER) was used for inferring regulator activity and ARACNE algorithm was conducted to construct TRNs and identify some MRs with DEGs from comparisons.
Functional analysis of DEGs and the module analysis of TRNs demonstrated that over-expressed EMP2 leads to a significant induction in the activity of regulators next to transcription factors and other genes implicated in vasculature development, cell proliferation, and protein kinase B signaling, whereas regulators near several genes of platelet activation vascular proliferation were repressed. Among these, PDGFA, ALDH1L2, BA1AP3, ANGPT1 and ST3GAL5 were found differentially expressed and significantly activitve in EMP2-over-expressed hRPECs versus vector control under hypoxia and may thus identified as MRs for EMP2-induced lesion under hypoxia.
MRs obtained in this study might serve as potential biomarkers for EMP2 induced lesion under hypoxia, illustrating gene expression landscapes which might be specific for diabetic retinopathy and might provide improved understanding of the disease.
将转录调控网络（TRN）的细胞特异性构建应用于 EMP2 诱导的血管增殖紊乱中鉴定其主调控因子（MRs），这方面的研究还很大程度上尚未探索。
使用 DESeq2 R 软件包对 EMP2 处理的 hRPECs 与载体对照（VC）或野生型（WT）hRPECs 的公共 RNA-seq 转录组数据进行差异表达基因（DEGs）分析。通过富集调控分析（VIPER）的虚拟推断蛋白活性用于推断调控活性，并且通过 ARACNE 算法构建 TRNs 并从比较中鉴定出一些具有 DEGs 的 MRs。
DEGs 的功能分析和 TRNs 的模块分析表明，过表达的 EMP2 导致紧邻转录因子和其他与血管发育、细胞增殖和蛋白激酶 B 信号传导相关的基因的调控因子的活性显著增加，而几个血小板激活血管增殖基因附近的调控因子受到抑制。在这些基因中，PDGFA、ALDH1L2、BA1AP3、ANGPT1 和 ST3GAL5 在 EMP2 过表达的 hRPECs 中表现出差异表达且在低氧条件下相对于 VC 显著激活，因此可能被鉴定为 EMP2 诱导低氧损伤的 MRs。
本研究获得的 MRs 可能作为 EMP2 诱导低氧损伤的潜在生物标志物，说明了可能是糖尿病性视网膜病变特有的基因表达图谱，并可能提供对该疾病的更好理解。
