Xu Wan, Wu Hongyan, Shang Lixin
The Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
Department of Obstetrics and Gynecology, PLA Army General Hospital, No.5 Nanmencang, Dongcheng District, Beijing, 100700, China.
BMC Pharmacol Toxicol. 2019 Feb 15;20(1):12. doi: 10.1186/s40360-019-0288-8.
This study aimed to identify potential zinc status indicators and to clarify the mechanisms underlying zinc deficiency-induced organ damage and mortality in mice.
The dataset GSE97112, including placental tissues of mice fed diets containing normal and low concentrations of zinc, was downloaded and preprocessed. Differentially expressed genes (DEGs) were calculated and identified for zinc deficiency-related gene clusters by using the weighed gene co-expression network analysis (WGCNA) algorithm. The Gene Ontology (GO)-Biological Process (BP) and KEGG pathway of genes in the zinc deficiency-related WGCNA modules were analyzed, and the protein-protein interaction (PPI) network was constructed. In addition, modules of the PPI network were identified, and transcription factors (TFs) and miRNAs regulating DEGs were predicted. Finally, drug-gene interactions were selected.
A total of 1055 DEGs containing 586 up- and 469 down-regulated genes were obtained. Three modules based on WGCNA had high correlation with degree of zinc deficiency. Annexin A1 (ANXA1), C-C motif chemokine receptor 3 (CCR3), C-X-C motif chemokine receptor 2 (CXCR2), and interleukin 2 (IL-2) were hub nodes in the PPI network. Three modules in the PPI network were identified, including module 1 associated with olfactory conduction and module 2 associated with inflammatory response. ANXA1, CCR3, and IL-2 were regulated by TFs. In addition, CXCR2, ANXA, and IL-2 were drug targets.
CXCR2, ANXA1, and CCR3 as well as olfactory receptor-related genes (proteins) may be used as biomarkers to assess zinc status in mice.
本研究旨在确定潜在的锌状态指标,并阐明锌缺乏诱导小鼠器官损伤和死亡的潜在机制。
下载并预处理数据集GSE97112,该数据集包含喂食正常和低锌浓度饮食的小鼠的胎盘组织。使用加权基因共表达网络分析(WGCNA)算法计算并鉴定锌缺乏相关基因簇的差异表达基因(DEG)。分析锌缺乏相关WGCNA模块中基因的基因本体(GO)-生物学过程(BP)和KEGG通路,并构建蛋白质-蛋白质相互作用(PPI)网络。此外,鉴定PPI网络的模块,并预测调节DEG的转录因子(TF)和微小RNA(miRNA)。最后,选择药物-基因相互作用。
共获得1055个DEG,其中包括586个上调基因和469个下调基因。基于WGCNA的三个模块与锌缺乏程度高度相关。膜联蛋白A1(ANXA1)、C-C基序趋化因子受体3(CCR3)、C-X-C基序趋化因子受体2(CXCR2)和白细胞介素2(IL-2)是PPI网络中的枢纽节点。鉴定了PPI网络中的三个模块,包括与嗅觉传导相关的模块1和与炎症反应相关的模块2。ANXA1、CCR3和IL-2受TF调节。此外,CXCR2、ANXA和IL-2是药物靶点。
CXCR2、ANXA1和CCR3以及嗅觉受体相关基因(蛋白质)可作为评估小鼠锌状态的生物标志物。