Search

Background Type 1 diabetes (T1D), an autoimmune disease, occurs most commonly in children. Identifying altered gene expression in peripheral blood mononuclear cells (PBMCs) of T1D may lead to new strategies for preserving or improving β-ell function in patients with T1D. Methods The Gene Expression Omnibus database was searched for microarray studies in PBMCs of T1D. Subsequently, gene expression datasets from multiple microarray studies were integrated to obtain differentially expressed genes (DEGs) between T1D and normal controls (NC). Gene function analysis was performed to determine the functions of the DEGs identified. Results Four microarray studies were available for analysis, including 199 T1D samples and 74 NC samples. Analysis revealed 695 genes that were significantly differentially expressed in PBMCs from T1D compared with NC samples, with 450 upregulated and 245 downregulated. Signal transduction (gene ontology [GO]: 0007165; false discovery rate [FDR] = 1.54 × 10–7) and protein binding (GO: 0005515; FDR = 2.93 × 10–24) were significantly enriched for the GO categories of biological processes and molecular functions, respectively. The most significant pathway in the Kyoto Encyclopedia of Genes and Genomes analysis was arachidonic acid metabolism (FDR = 1.44 × 10–3). Protein–protein interaction network analysis showed that the significant hub proteins contained immature colon carcinoma transcript 1 (ICT1; degree = 214; clustering coefficient [C] = 4.39 × 10–5), zinc finger and BTB domain containing 16 (ZBTB16; degree = 112; C = 8.04 × 10–4), and SERTA domain containing 1 (SERTAD1; degree = 38; C = 0.0014). Conclusions This integrated analysis will help develop improved therapies and interventions for T1D by identifying novel drug targets.

Type 1 diabetes (T1D), an autoimmune disease, occurs most commonly in children. Identifying altered gene expression in peripheral blood mononuclear cells (PBMCs) of T1D may lead to new strategies for preserving or improving β-ell function in patients with T1D.The Gene Expression Omnibus database was searched for microarray studies in PBMCs of T1D. Subsequently, gene expression datasets from multiple microarray studies were integrated to obtain differentially expressed genes (DEGs) between T1D and normal controls (NC). Gene function analysis was performed to determine the functions of the DEGs identified.Four microarray studies were available for analysis, including 199 T1D samples and 74 NC samples. Analysis revealed 695 genes that were significantly differentially expressed in PBMCs from T1D compared with NC samples, with 450 upregulated and 245 downregulated. Signal transduction (gene ontology [GO]: 0007165; false discovery rate [FDR] = 1.54 × 10This integrated analysis will help develop improved therapies and interventions for T1D by identifying novel drug targets.

Background Atherosclerosis is a chronic degenerative disease of the arteries and is thought to be one of the most common causes of death globally. In recent years, the functions of adventitial fibroblasts in the development of atherosclerosis and tissue repair have gained increased interests. LPS can increase the morbidity and mortality of atherosclerosis-associated cardiovascular disease. Although LPS increases neointimal via TLR4 activation has been reported, how LPS augments atherogenesis through acting on adventitial fibroblasts is still unknown. Here we explored lipid deposition within adventitial fibroblasts mediated by lipopolysaccharide (LPS) to imitate inflammatory conditions. Results In our study, LPS enhanced lipid deposition by the up-regulated expression of adipose differentiation-related protein (ADRP) as the silencing of ADRP abrogated lipid deposition in LPS-activated adventitial fibroblasts. In addition, pre-treatment with anti-Toll-like receptor 4 (TLR4) antibody diminished the LPS-induced lipid deposition and ADRP expression. Moreover, LPS induced translocation of nuclear factor-κB (NF-κB), which could markedly up-regulate lipid deposition as pre-treatment with the NF-κB inhibitor, PDTC, significantly reduced lipid droplets. In addition, the lowering lipid accumulation was accompanied with the decreased ADRP expression. Furthermore, LPS-induced adventitial fibroblasts secreted more monocyte chemoattractant protein (MCP-1), compared with transforming growth factor-β1 (TGF-β1). Conclusions Taken together, these results suggest that LPS promotes lipid accumulation via the up-regulation of ADRP expression through TLR4 activated downstream of NF-κB in adventitial fibroblasts. Increased levels of MCP-1 released from LPS-activated adventitial fibroblasts and lipid accumulation may accelerate monocytes recruitment and lipid-laden macrophage foam cells formation. Here, our study provides a new explanation as to how bacterial infection contributes to the pathological process of atherosclerosis.