Differential gene expression profiling of the sciatic nerve in type 1 and type 2 diabetic mice

Abstract

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.

Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes

“…We also found the RNA gene ERICH3-AS1 to be highly downregulated in patients with type 2 diabetes. Consistent with our findings, this gene is downregulated in a sciatic nerve in diabetic mice [83]. Little is known about the function of ERICH3, however it is highly expressed in airway cilia and has been associated with major depressive disorder [84,85].…”

Gene Expression Profiling of the Sciatic Nerve in Streptozotocin-Induced Diabetic Rats with Peripheral Neuropathy

“…Functional enrichment analyses indicated that they were associated with "cell division," "protein phosphorylation," and "cell cycle." This is in accordance with the study by Gu et al, in which a number of DEGs identified from the sciatic nerve of type 1 diabetic mice were enriched in the BP item "cell proliferation" [14]. They considered that the abnormal pain responses in neuropathic pain were associated with the proliferation of nerve cells including microglia and astrocyte.…”

Integrative analysis of host omics and microbiome data provides hints at common pathways and biomarkers for diabetes risk

“…Similarly, the interleukin 1 receptor antagonist protein (IL1RAP) was upregulated and was previously described as a biomarker for insulin resistance and has been shown to decrease insulin sensitivity [51,52]. Furthermore, the Elongation of very long chain fatty acids protein 2 (ELOVL2) was downregulated in T2D mice and was previously reported as a differentially expressed gene associated with diabetic peripheral neuropathy (DPN) in the sciatic nerve of T1D and T2D mice [53]. Finally, the Resistin cytokine and the Clostridium cluster IV bacteria were identi ed as important T2D-related biomarkers in our analysis.…”