BACKGROUND This study aimed to identify potential zinc status indicators and to clarify the mechanisms underlying zinc deficiency-induced organ damage and mortality in mice. METHODS 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. RESULTS 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. CONCLUSION CXCR2, ANXA1, and CCR3 as well as olfactory receptor-related genes (proteins) may be used as biomarkers to assess zinc status in mice.

中文翻译：

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从微阵列数据中鉴定用于评估小鼠妊娠期间锌状态的新候选指标。


背景本研究旨在确定潜在的锌状态指标，并阐明缺锌引起的小鼠器官损伤和死亡的机制。方法 下载并预处理数据集 GSE97112，包括喂食含有正常和低浓度锌的饮食的小鼠的胎盘组织。采用加权基因共表达网络分析（WGCNA）算法计算并鉴定缺锌相关基因簇的差异表达基因（DEG）。分析缺锌相关WGCNA模块中基因的基因本体（GO）-生物过程（BP）和KEGG通路，构建蛋白质-蛋白质相互作用（PPI）网络。此外，还确定了 PPI 网络的模块，并预测了调节 DEG 的转录因子 (TF) 和 miRNA。最后，选择药物-基因相互作用。结果共获得1055个DEG，其中包含586个上调基因和469个下调基因。基于WGCNA的三个模块与缺锌程度具有高度相关性。膜联蛋白 A1 (ANXA1)、CC 基序趋化因子受体 3 (CCR3)、CXC 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。确定了 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。结论 CXCR2、ANXA1 和 CCR3 以及嗅觉受体相关基因（蛋白质）可用作评估小鼠锌状态的生物标志物。