Characterization of the Phosphoproteome in SLE Patients

Zhang, Xinzhou; Ma, Hualin; Huang, Jianrong; Dai, Yong

doi:10.1371/journal.pone.0053129

Cited by 8 publications

(8 citation statements)

References 32 publications

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“…Besides the autoimmune inflammation mediated by IFNa, the blue and yellow modules related to aberrant multicellular organismal processes in PBMC of SLE were also identified by the WGCNA, including the metabolism, cell development, ion transport, signaling transduction, and so on. Zhang et al performed a GO analysis of genes corresponding to differentially expressed proteins in SLE and also found cellular component organization, transport and multicellular organismal processes were significantly enriched, consistent with our analysis (38). For a long time, we focused on the IFN and autoimmune inflammation in SLE.…”

Section: Type I Ifn Inflammatory Response Cellular Organismal Processes In Slesupporting

confidence: 86%

Exploration of the Shared Gene Signatures and Molecular Mechanisms Between Systemic Lupus Erythematosus and Pulmonary Arterial Hypertension: Evidence From Transcriptome Data

et al. 2021

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BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease that can affect multiple systems. Pulmonary arterial hypertension (PAH) has a close linkage with SLE. However, the inter-relational mechanisms between them are still unclear. This article aimed to explore the shared gene signatures and potential molecular mechanisms in SLE and PAH.MethodsThe microarray data of SLE and PAH in the Gene Expression Omnibus (GEO) database were downloaded. The Weighted Gene Co-Expression Network Analysis (WGCNA) was used to identify the co-expression modules related to SLE and PAH. The shared genes existing in the SLE and PAH were performed an enrichment analysis by ClueGO software, and their unique genes were also performed with biological processes analyses using the DAVID website. The results were validated in another cohort by differential gene analysis. Moreover, the common microRNAs (miRNAs) in SLE and PAH were obtained from the Human microRNA Disease Database (HMDD) and the target genes of whom were predicted through the miRTarbase. Finally, we constructed the common miRNAs–mRNAs network with the overlapped genes in target and shared genes. ResultsUsing WGCNA, four modules and one module were identified as the significant modules with SLE and PAH, respectively. A ClueGO enrichment analysis of shared genes reported that highly activated type I IFN response was a common feature in the pathophysiology of SLE and PAH. The results of differential analysis in another cohort were extremely similar to them. We also proposed a disease road model for the possible mechanism of PAH secondary to SLE according to the shared and unique gene signatures in SLE and PAH. The miRNA–mRNA network showed that hsa-miR-146a might regulate the shared IFN-induced genes, which might play an important role in PAH secondary to SLE.ConclusionOur work firstly revealed the high IFN response in SLE patients might be a crucial susceptible factor for PAH and identified novel gene candidates that could be used as biomarkers or potential therapeutic targets.

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Section: Type I Ifn Inflammatory Response Cellular Organismal Processes In Slesupporting

confidence: 86%

Exploration of the Shared Gene Signatures and Molecular Mechanisms Between Systemic Lupus Erythematosus and Pulmonary Arterial Hypertension: Evidence From Transcriptome Data

et al. 2021

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“…Interestingly, comparative network analysis of the phosphoproteomes of peripheral blood mononuclear cells of SLE patients versus healthy controls described PKCδ (beside Src kinases, the NF-kB signaling component RelA and HDAC1) as one of the genes with the most connections to other proteins in the altered network of SLE patients and therefore with significant role in the network stability [ 53 ].…”

Section: Pkcδ In Human Systemic Lupus Erythematosusmentioning

confidence: 99%

Protein Kinase C δ: a Gatekeeper of Immune Homeostasis

et al. 2016

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Human autoimmune disorders present in various forms and are associated with a life-long burden of high morbidity and mortality. Many different circumstances lead to the loss of immune tolerance and often the origin is suspected to be multifactorial. Recently, patients with autosomal recessive mutations in PRKCD encoding protein kinase c delta (PKCδ) have been identified, representing a monogenic prototype for one of the most prominent forms of humoral systemic autoimmune diseases, systemic lupus erythematosus (SLE). PKCδ is a signaling kinase with multiple downstream target proteins and with functions in various signaling pathways. Interestingly, mouse models have indicated a special role of the ubiquitously expressed protein in the control of B-cell tolerance revealed by the severe autoimmunity in Prkcd−/− knockout mice as the major phenotype. As such, the study of PKCδ deficiency in humans has tremendous potential in enhancing our knowledge on the mechanisms of B-cell tolerance.

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“…As described in detail previously [ 18 ], we mapped differentially modified genes to the KEGG pathway database using GenMAPP v2.1 and then performed a statistical test to identify enriched metabolic pathways. miR-146a-5p was significantly up-regulated in both the cell group and exosome group.…”

Section: Resultsmentioning

confidence: 99%

Analysis of differentially expressed microRNA of TNF-α-stimulated mesenchymal stem cells and exosomes from their culture supernatant

Ma¹,

Zhang²,

Xü³

et al. 2018

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IntroductionTo analyze the microRNA expression of tumor necrosi factor α (TNF-α) stimulated mesenchymal stem cells (MSCs) and exosomes from their culture supernatant.Material and methodsTNF-α (20 ng/ml) was used to stimulate MSCs, which were then regarded as TNF-α cells (TC), while unstimulated cells were the normal control cells (NCC). MSCs and their culture supernatant were harvested after 48 h. Subsequently, exosomes were isolated from culture supernatants with ExoQuick-TC and were divided into two groups, TNF-α exosomes (TE) and normal control exosomes (NCE). Then, the microRNAs were measured by high-throughput sequencing and the results were differentially analyzed. Finally, the correlation of the target genes corresponding to differently expressed microRNAs was analyzed by gene ontology (GO) and KEGG pathway analysis.ResultsHigh-throughput sequencing showed that the cellular compartment (TC vs. NCC) had 280 microRNAs. miR-146a-5p was a uniquely up-regulated microRNA (p < 0.001) and the most significantly down-regulated microRNA among the 279 microRNAs included was miR-150-5p (p < 0.001). There were 180 differentially expressed microRNAs in the exosome compartment (TE vs. NCE), where miR-146-5p (p < 0.001) was one of 176 upregulated microRNAs and miR-203b-5p (p < 0.001) was one of 4 downregulated microRNAs. Coincidentally, bioinformatics analysis showed that IRAK1 was a critical target gene of miR-146-5p related to the Toll-like receptor (TLR) signaling pathway.ConclusionsIn contrast with the control group, there were significantly differentially expressed microRNAs in both MSCs and exosomes. Interestingly, miR-146a-5p was up-regulated in both comparative groups, and its target gene IRAK1 plays a crucial part in the TLR signaling pathway. These investigations demonstrate a new direction for subsequent inflammation mechanistic studies.

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Characterization of the Phosphoproteome in SLE Patients

Cited by 8 publications

References 32 publications

Exploration of the Shared Gene Signatures and Molecular Mechanisms Between Systemic Lupus Erythematosus and Pulmonary Arterial Hypertension: Evidence From Transcriptome Data

Exploration of the Shared Gene Signatures and Molecular Mechanisms Between Systemic Lupus Erythematosus and Pulmonary Arterial Hypertension: Evidence From Transcriptome Data

Protein Kinase C δ: a Gatekeeper of Immune Homeostasis

Analysis of differentially expressed microRNA of TNF-α-stimulated mesenchymal stem cells and exosomes from their culture supernatant

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