Differential gene expression profiling of the sciatic nerve in type 1 and type 2 diabetic mice.
Differential gene expression profiling of the sciatic nerve in type 1 and type 2 diabetic mice.
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1型和2型糖尿病小鼠坐骨神经的差异基因表达谱
DOI：
10.3892/br.2018.1135
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发表时间：
2018-10
影响因子：
2.3
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Gu Y;Qiu ZL;Liu DZ;Sun GL;Guan YC;Hei ZQ;Li X
糖尿病周围神经病变（DPN）是糖尿病（DM）的常见并发症。1型（T1）和2型（T2）DM的DPN发病机制和所需的治疗干预可能不同。然而，这两种类型糖尿病DPN发病机制的分子机制仍不清楚。本研究的目的是利用生物信息学分析确定T1和T2 DM小鼠坐骨神经中与DPN相关的基因和通路的变化。从Gene Expression Omnibus数据库下载T1 DM（GSE 11343）和T2 DM（GSE 27382）小鼠模型的坐骨神经的微阵列谱，以鉴定每个模型中的差异表达基因（DEG）。采用BRB-ArrayTools软件对两种类型糖尿病（变化倍数≥2且P<0.05）的DEG进行了鉴定。基因本体（GO）术语和京都基因和基因组百科全书（KEGG）途径富集分析使用用于注释、可视化和集成发现的数据库进行。使用检索相互作用基因/蛋白质的搜索工具构建蛋白质-蛋白质相互作用（PPI）网络，并使用Cytoscape可视化。与对照样品相比，在T1和T2 DM小鼠的坐骨神经中分别鉴定出623和1，890个DEG。其中，75个基因在两种模型的坐骨神经中协调失调。T1 DM小鼠特有的许多DEG定位于核质并与转录过程的调节相关，而T2 DM小鼠特有的许多DEG定位于细胞连接处并与离子转运相关。此外，某些DEG可能与用于两种类型DM的不同治疗策略相关。该分析提供了对T1和T2 DM中坐骨神经中的功能基因集和通路的深入了解。这些结果将提高对DPN病理生理学基础的分子机制的理解，并为每种类型DM的DPN治疗策略的发展提供信息。
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). The pathogenic mechanisms of DPN and the therapeutic interventions required may be distinct between type 1 (T1) and type 2 (T2) DM. However, the molecular mechanisms underlying the pathogenesis of DPN in both types of diabetes remain unclear. The aim of the current study was to identify the changes in genes and pathways associated with DPN in sciatic nerves of T1- and T2DM mice using bioinformatics analysis. The microarray profiles of sciatic nerves of T1DM (GSE11343) and T2DM (GSE27382) mouse models were downloaded from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) in each. DEGs in the two types of DM (with fold change ≥2 and P<0.05) were identified with BRB-ArrayTools. Gene Ontology (GO) term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery. A protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins and visualized using Cytoscape. Compared with control samples, 623 and 1,890 DEGs were identified in sciatic nerves of T1- and T2DM mice, respectively. Of these, 75 genes were coordinately dysregulated in the sciatic nerves of both models. Many DEGs unique to T1DM mice were localized to the nucleoplasm and were associated with regulation of transcription processes, while many unique to T2DM mice were localized at cell junctions and were associated with ion transport. In addition, certain DEGs may be associated with the different treatment strategies used for the two types of DM. This analysis provides insight into the functional gene sets and pathways operating in sciatic nerves in T1- and T2DM. The results should improve understanding of the molecular mechanisms underlying the pathophysiology of DPN, and provide information for the development of therapeutic strategies for DPN specific to each type of DM.