Department of Obstetrics and Gynecology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Gastroenterology Department, Harbin The First Hospital, Harbin, Heilongjiang 150001, P.R. China.
Mol Med Rep. 2018 Mar;17(3):3697-3707. doi: 10.3892/mmr.2017.8330. Epub 2017 Dec 20.
Maternal diabetes has been reported to be a critical factor for congenital heart defects (CHD) in offspring. The present study aimed to screen the key genes that may be involved in CHD in offspring of diabetic mothers. The present study obtained the gene expression profile of GSE32078, including three embryonic heart tissue samples at embryonic day 13.5 (E13.5), three embryonic heart tissue samples at embryonic day 15.5 (E15.5) from diabetic mice and their respective controls from normal mice. The cut‑off criterion of P<0.08 was set to screen differentially expressed genes (DEGs). Their enrichment functions were predicted by Gene Ontology. The enriched pathways were forecasted by Kyoto Encyclopedia of Genes and Genomes and Reactome analysis. Protein‑protein interaction (PPI) networks for DEGs were constructed using Cytoscape. The present study identified 869 and 802 DEGs in E13.5 group and E15.5 group, respectively and 182 DEGs were shared by the two developmental stages. The pathway enrichment analysis results revealed that DEGs including intercellular adhesion molecule 1 (Icam1) and H2‑M9 were enriched in cell adhesion molecules; DEGs including bone morphogenetic protein receptor type 1A, transforming growth factor β receptor 1 and SMAD specific E3 ubiquitin protein ligase 1 were enriched in the tumor growth factor‑β signaling pathway. In addition, DEGs including Icam1, C1s and Fc fragment of IgG receptor IIb were enriched in Staphylococcus aureus infection. Furthermore, the shared DEGs including Icam1, nuclear receptor corepressor 1 (Ncor1) and AKT serine/threonine kinase 3 (Akt3) had high connectivity degrees in the PPI network. The shared DEGs including Icam1, Ncor1 and Akt3 may be important in the cardiogenesis of embryos. These genes may be involved in the development of CHD in the offspring of diabetic mothers.
母体糖尿病已被报道为后代先天性心脏病(CHD)的关键因素。本研究旨在筛选可能与糖尿病母亲后代 CHD 相关的关键基因。本研究从糖尿病小鼠和正常小鼠的胚胎 13.5 天(E13.5)和胚胎 15.5 天(E15.5)的三个胚胎心脏组织样本中获得了 GSE32078 的基因表达谱。将 P<0.08 的截止标准设置为筛选差异表达基因(DEGs)。通过基因本体论预测其富集功能。通过京都基因与基因组百科全书和反应组分析预测富集途径。使用 Cytoscape 构建 DEGs 的蛋白质-蛋白质相互作用(PPI)网络。本研究分别在 E13.5 组和 E15.5 组中鉴定出 869 个和 802 个 DEGs,两个发育阶段共有 182 个 DEGs。通路富集分析结果表明,包括细胞间黏附分子 1(Icam1)和 H2-M9 在内的 DEGs 富集在细胞黏附分子中;包括骨形态发生蛋白受体 1A、转化生长因子-β受体 1 和 SMAD 特异性 E3 泛素蛋白连接酶 1 在内的 DEGs 富集在肿瘤生长因子-β信号通路中。此外,包括 Icam1、C1s 和 IgG 受体 IIb Fc 片段在内的 DEGs 富集在金黄色葡萄球菌感染中。此外,PPI 网络中具有高连接度的共享 DEGs 包括 Icam1、核受体共抑制因子 1(Ncor1)和 AKT 丝氨酸/苏氨酸激酶 3(Akt3)。共享的 DEGs 包括 Icam1、Ncor1 和 Akt3 可能在胚胎心脏发生中很重要。这些基因可能参与了糖尿病母亲后代 CHD 的发生发展。