Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods.
Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods.
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生物信息学方法预测糖尿病肾病的分子机制和潜在治疗靶点
DOI：
10.3892/ijmm.2016.2527
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发表时间：
2016-05
影响因子：
5.4
通讯作者：
Xu ZG
中科院分区：
文献类型：
--
作者：
Wang WN;Zhang WL;Zhou GY;Ma FZ;Sun T;Su SS;Xu ZG
本研究旨在探讨糖尿病肾病（DN）的分子机制及影响DN的遗传因素。从GEO数据库（登录号GSE 20844）获得与DN相关的基因表达谱。筛选糖尿病小鼠与非糖尿病小鼠的差异表达基因。随后，对DEG进行功能和通路分析。构建了蛋白质相互作用网络，并从蛋白质相互作用网络中筛选转录因子。共筛选出92个上调基因和118个下调基因。通路分析显示p53信号通路、转化生长因子（TGF）-β信号通路和丝裂原活化蛋白激酶（MAPK）信号通路被上调的基因显著富集。Serpine 1（也称为纤溶酶原激活物抑制剂-1）、早期生长反应1（Egr 1）和Mdk通过三种方法被发现是PPI网络中的重要节点。共发现12个TF差异表达，其中核受体亚家族4，A组，成员1（Nr 4a 1）和过氧化物酶体增殖物激活受体γ（Pparg）被发现与其他DEG有多种相互作用。我们证实了p53信号通路、TGF-β信号通路和MAPK信号通路在糖尿病小鼠中失调。这些重要的神经节（Serpine 1、Egr 1和Mdk）和差异表达的转录因子（Nr 4a 1和Pparg）可能为DN的靶向治疗提供新的途径。
In this study, we aimed to explore the molecular mechanisms of and genetic factors influencing diabetic nephropathy (DN). Gene expression profiles associated with DN were obtained from the GEO database (Accession no. GSE20844). The differentially expressed genes (DEGs) between diabetic mice and non-diabetic mice were screened. Subsequently, the DEGs were subjected to functional and pathway analysis. The protein-protein interaction (PPI) network was constructed and the transcription factors (TFs) were screened among the DEGs. A total of 92 upregulated and 118 downregulated genes were screened. Pathway analysis revealed that the p53 signaling pathway, the transforming growth factor (TGF)-β signaling pathway and the mitogen-activated protein kinase (MAPK) signaling pathway were significantly enriched by upregulated genes. Serpine1 (also known as plasminogen activator inhibitor-1), early growth response 1 (Egr1) and Mdk were found to be significant nodes in the PPI network by three methods. A total of 12 TFs were found to be differentially expressed, of which nuclear receptor subfamily 4, group A, member 1 (Nr4a1) and peroxisome proliferator-activated receptor gamma (Pparg) were found to have multiple interactions with other DEGs. We demonstrated that the p53 signaling pathway, the TGF-β signaling pathway and the MAPK signaling pathway were dysregulated in the diabetic mice. The significant nodes (Serpine1, Egr1 and Mdk) and differentially expressed TFs (Nr4a1 and Pparg) may provide a novel avenue for the targeted therapy of DN.