Diabetes, Metabolic Syndrome and Obesity (Jun 2019)
Identification of dynamic molecular networks in peripheral blood mononuclear cells in type 1 diabetes mellitus
Abstract
Lu Li,1,* Zongfu Pan,2,* Xi Yang11Department of Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Pharmacy, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this work Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by the immune destruction of islet β cells. Gene expression in peripheral blood mononuclear cells (PBMCs) could offer new disease and treatment markers in T1DM. The objective of this study was to explore the coexpression and dynamic molecular networks in PBMCs of T1DM patients.Methods: Dataset GSE9006 contains PBMC samples of healthy volunteers, newly diagnosed T1DM patients, T1DM patients after insulin treatment, and newly diagnosed type 2 diabetes mellitus (T2DM) patients. Weighted correlation network analysis (WGCNA) was used to generate coexpression networks in T1DM and T2DM. Functional pathways in highly correlated modules of T1DM were enriched by gene set enrichment analysis (GSEA). We next filtered the differentially expressed genes (DEGs) and revealed their dynamic expression profiles in T1DM with or without insulin treatment. Furthermore, dynamic clusters and dynamic protein–protein interaction networks were identified. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was developed in dynamic clusters.Results: WGCNA disclosed 12 distinct gene modules, and distinguished between correlated networks in T1DM and T2DM. Two modules were closely associated with T1DM. GSEA showed that the immune response and response to cytokines were enriched in the T1DM highly correlated module. Next, we screened 44 DEGs in newly diagnosed T1DM compared with healthy donors, and 71 DEGs in 1-month and 97 DEGs in 4-month insulin treatment groups compared with newly diagnosed T1DM. Dynamic expression profiles of DEGs indicated the potential targets for T1DM treatment. Moreover, four molecular dynamic clusters were analyzed in newly diagnosed and insulin-treated T1DM. Functional annotation showed that these clusters were mainly enriched in the IL-17 signaling pathway, nuclear factor-ϰB signaling pathway, and tumor necrosis factor signaling pathway.Conclusion: The results indicate potential drug targets or clinical efficacy markers, as well as demonstrating the underlying molecular mechanisms of T1DM treatment.Keywords: type 1 diabetes mellitus, dynamic molecular networks, coexpression networks, peripheral blood mononuclear cells
