SLEAR predisposes to systemic lupus erythematosus by regulating apoptosis [ChIRP-Seq]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE104479 | GEO | 2018/04/09
REPOSITORIES: GEO
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Project description:Systemic lupus erythematosus (SLE) is an autoimmune disease, and affects all parts of the human body. Genome-wide association studies have been employed to identify susceptibility genes of SLE. However, most of the SLE associated variants are located in the noncoding regions of the human genome. We characterized SLE risk variants in Chinese populations. One of the most significant validated SNP was located in a gene which we named SLEAR. We found SLEAR was enriched in the nucleus and could regulate apoptosis. Apoptosis is a highly regulated process. And misregulation of the process could lead to autoimmune diseases, especially SLE. Our results suggest that SLEAR plays a key role in apoptosis regulation and is associated with SLE predisposition.
2018-04-09 | GSE104382 | GEO
Project description:Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Knowledge of circulating immune cell types and cell states associated with SLE remains incomplete. We profiled over 1.2 million PBMCs (162 cases, 99 controls) with multiplexed single-cell RNA-seq (mux-seq). Cases exhibited prominent expression of type-1 interferon-stimulated genes (ISG) in monocytes, reduction of naïve CD4+ T cells that correlated with monocyte ISG expression, and expansion of repertoire-restricted cytotoxic GZMH+ CD8+ T cells. Cell-type-specific expression features accurately predicted case-control status and stratified patients into two molecular subtypes. We integrated dense genotyping data, mapping cell-type-specific cis-eQTLs and linked known and novel SLE-associated variants to cell-type-specific gene expression. These results demonstrate mux-seq as a systematic approach to characterize cellular composition, identify transcriptional signatures, and annotate genetic variants associated with SLE.
2021-12-01 | GSE174188 | GEO
Project description:SLEAR predisposes to systemic lupus erythematosus by regulating apoptosis [ChIRP-Seq]
| PRJNA412810 | ENA
Project description:Background: Systemic Lupus Erythematosus (SLE) is a prototype of autoimmune disease. Decreased cell numbers and suppressive defects of naturally occurring CD4+CD25+FOXP3+ regulatory T cells (Tregs) play an important role in the breakdown of SLE immune tolenrance. We have peviously observed significantly increased apoptosis of peripheral blood CD4+ T cells in SLE patients. Our objective here was to detect the apoptosis of Tregs in SLE patients to see if it could contribute to reduced suppressive activity of Tregs, and further elucidate the genes and signaling pathways which trigger the apoptosis in these cells. Methods and findings: The cell number and apoptosis rates of Tregs was respectively evaluated in SLE patients and normal controls (NCs) by FACS. The suppressive activity of Tregs was measured by coculture with CD4+CD25-CD127dim/- T cells. The relationship of abnormal Tregs apoptosis with clinical parameters was analyzed by Pearson correlation analysis. Gene expression profiles of unstimulated Tregs from active SLE patients and NCs were generated by microarray analysis. Differential genes expression was verified by real time-PCR. We found that the Tregs from SLE patients showed a significantly reduced number, elevated apoptosis rates and impared suppressive capacity compared to NCs. The increased apoptosis of Tregs was negatively correlated with the total number of Tregs and positively correlated with disease activities. Gene expression profiles of unstimulated Tregs from recent-onset SLE subjects reveal a cellular response that could make the cells sensitive to apoptosis, partially due to the stress responses, DNA-damaging and cytokine stimulation. This global picture of pathway-specific expression signatures is a step further into dissecting Tregs defects in the pathogenesis of SLE.
2023-04-03 | GSE154552 | GEO
Project description:MicroRNAs (miRNAs) have been implicated as fine-tuning regulators controlling diverse biological processes at the level of posttranscriptional repression. Dysregulation of miRNAs has been described in various disease states, including inflammatory autoimmune diseases. By using high-throughput microRNA profiling analysis, we identified a series of miRNAs dysregulated in local inflammatory lesions of human patients with autoimmune diseases such as SLE. We isolated the renal biopsy samples from eight SLE patients as well as tumor adjacent kidney tissues from four kidney cancer patients as controls for comparison. Total RNA was extracted for the TaqManM-BM-. Low Density Assay v3.0
2012-12-19 | E-GEOD-37426 | biostudies-arrayexpress
Project description:Systemic lupus erythematosus (SLE) is a systemic and heterogeneous autoimmune disease for which its treatment and phosphorylation-dependent regulatory mechanism remain elusive. Here, we aim to explore the molecular mechanism of phosphorylation regulation for SLE. We employed high-throughput Phosphoproteomics of peripheral blood mononuclear cells (PBMCs) from 126 patients with SLE remission stage (SLE_S), 70 patients with SLE active stage (SLE_A), 160 patients with RA, and 135 healthy controls (HC). An independent cohort that included 60 SLE_S, 35 SLE_A, 50 RA and 40 HC was used to validate the phosphosites via parallel reaction monitoring (PRM). We revealed upregulated pathways involved in cell adhesion and migration in patients with SLE (SLE_S and SLE_A) compared with HCs and RA. Expression pattern clustering analysis revealed several specifically upregulated phosphosites, and the leukocyte transendothelial migration was specifically enriched in SLE_A. We predicted several key kinases including MAP3Ks, MAP2Ks, IKKB and TBK1, and found that upregulated kinase activity is associated with increased phosphorylation of VCL, TLN1 and VAPB by kinases-substrate network analysis. These phosphorylated proteins also regulate the pathways related to cell adhesion and migration, and which have not been implicated in previous studies of SLE. Moreover, we validated these phosphosites with the same trend as 4D-LFQ data, including LCP1 S5, TLN1 S1201, TLN1 S1225, VCL S275 and VCL S579. In summary, the present study elucidates the changes of phosphosites, kinases and pathways in SLE, and may provide potentially novel targets for further mechanism exploration.
2023-03-11 | PXD025559 | Pride
Project description:Systemic lupus erythematosus (SLE) is a systemic and heterogeneous autoimmune disease for which its treatment and phosphorylation-dependent regulatory mechanism remain elusive. Here, we aim to explore the molecular mechanism of phosphorylation regulation for SLE. We employed high-throughput Phosphoproteomics of peripheral blood mononuclear cells (PBMCs) from 126 patients with SLE remission stage (SLE_S), 70 patients with SLE active stage (SLE_A), 160 patients with RA, and 135 healthy controls (HC). An independent cohort that included 60 SLE_S, 35 SLE_A, 50 RA and 40 HC was used to validate the phosphosites via parallel reaction monitoring (PRM). We revealed upregulated pathways involved in cell adhesion and migration in patients with SLE (SLE_S and SLE_A) compared with HCs and RA. Expression pattern clustering analysis revealed several specifically upregulated phosphosites, and the leukocyte transendothelial migration was specifically enriched in SLE_A. We predicted several key kinases including MAP3Ks, MAP2Ks, IKKB and TBK1, and found that upregulated kinase activity is associated with increased phosphorylation of VCL, TLN1 and VAPB by kinases-substrate network analysis. These phosphorylated proteins also regulate the pathways related to cell adhesion and migration, and which have not been implicated in previous studies of SLE. Moreover, we validated these phosphosites with the same trend as 4D-LFQ data, including LCP1 S5, TLN1 S1201, TLN1 S1225, VCL S275 and VCL S579. In summary, the present study elucidates the changes of phosphosites, kinases and pathways in SLE, and may provide potentially novel targets for further mechanism exploration.
2023-03-11 | PXD025076 | Pride
Project description:Systemic lupus erythematosus (SLE) is a systemic and heterogeneous autoimmune disease for which its treatment and phosphorylation-dependent regulatory mechanism remain elusive. Here, we aim to explore the molecular mechanism of phosphorylation regulation for SLE. We employed high-throughput Phosphoproteomics of peripheral blood mononuclear cells (PBMCs) from 126 patients with SLE remission stage (SLE_S), 70 patients with SLE active stage (SLE_A), 160 patients with RA, and 135 healthy controls (HC). An independent cohort that included 60 SLE_S, 35 SLE_A, 50 RA and 40 HC was used to validate the phosphosites via parallel reaction monitoring (PRM). We revealed upregulated pathways involved in cell adhesion and migration in patients with SLE (SLE_S and SLE_A) compared with HCs and RA. Expression pattern clustering analysis revealed several specifically upregulated phosphosites, and the leukocyte transendothelial migration was specifically enriched in SLE_A. We predicted several key kinases including MAP3Ks, MAP2Ks, IKKB and TBK1, and found that upregulated kinase activity is associated with increased phosphorylation of VCL, TLN1 and VAPB by kinases-substrate network analysis. These phosphorylated proteins also regulate the pathways related to cell adhesion and migration, and which have not been implicated in previous studies of SLE. Moreover, we validated these phosphosites with the same trend as 4D-LFQ data, including LCP1 S5, TLN1 S1201, TLN1 S1225, VCL S275 and VCL S579. In summary, the present study elucidates the changes of phosphosites, kinases and pathways in SLE, and may provide potentially novel targets for further mechanism exploration.
2023-03-11 | PXD025399 | Pride
Project description:Genome-wide association studies implicate multiple loci in risk for systemic lupus erythematosus (SLE), but few contain exonic variants, rendering systematic identification of non-coding variants essential to decoding SLE genetics. We utilized SNP-seq and bioinformatic enrichment to interrogate 2180 single-nucleotide polymorphisms (SNPs) from 87 SLE risk loci for potential binding of transcription factors and related proteins from B cells. 52 SNPs that passed initial screening were tested by electrophoretic mobility shift (EMSA) and luciferase reporter assays. To identify binding of transcription factors and/or other nuclear proteins in an allele-determined manner, we employed pulldown using nuclear extract from Daudi cells and silver staining in SNPs that had exhibited allele-specific differential binding by EMSA. Each pulldown product for each allele of the five high-probability SNPs (rs2297550 C/G, rs13213604 C/G, rs276461 T/C, rs9907955 C/T, rs7302634 T/C) was evaluated by mass spectrometry (MS) to identify binding nuclear proteins, yielding a set of candidate proteins for each.
2024-08-02 | PXD048367 | Pride
Project description:The role of metabolomics in autoimmune diseases has been a rapidly expanding area in researches over the last decade, while its pathophysiologic impact on systemic lupus erythematosus (SLE) remains poorly elucidated. In this study, we analyzed the metabolic profiling of fecal samples from SLE patients and healthy controls based on ultra-high-performance liquid chromatography equipped with mass spectrometry for exploring the potential biomarkers of SLE. The results showed that 23 differential metabolites and 5 perturbed pathways were identified between the two groups, including aminoacyl-tRNA biosynthesis, thiamine metabolism, nitrogen metabolism, tryptophan metabolism, and cyanoamino acid metabolism. In addition, logistic regression and ROC analysis were used to establish a diagnostic model for distinguishing SLE patients from healthy controls. The combined model of fecal PG 27:2 and proline achieved an area under the ROC curve of 0.846, and had a good diagnostic efficacy. In the present study, we analyzed the correlations between fecal metabolic perturbations and SLE pathogenesis. In summary, we firstly illustrate the comprehensive metabolic profiles of feces in SLE patients, suggesting that the fecal metabolites could be used as the potential non-invasive biomarkers for SLE.
2020-01-30 | MTBLS916 | MetaboLights