Mus musculus
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ABSTRACT:
PROVIDER: PRJNA126533 | ENA |
REPOSITORIES: ENA
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Project description:To identify any differentially expressed miRNAs in the CD4+ T cells of lupus. 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 human lupus. By using high-throughput microRNA profiling analysis, we identified that two miRNAs (miR-21 and miR-148a) overexpressed in CD4+ T cells from both lupus patients and lupus-prone MRL/lpr mice,which promote cell hypomethylation by repressing DNA methyltransferase 1 (DNMT1) expression. We isolated the splenic CD4+ T cells and B cells from MRL/lpr mice at 5 and 16 weeks of age.Cells were collected and total RNA was extracted for the TaqMan® Low Density Assay v2.0 Normalization was performed with snoRNA202, reference snRNAs for mouse.Comparative real-time PCR was performed in triplicate, including no-template.controls. Relative expression was calculated with the comparative cycle threshold method.
2010-07-06 | E-GEOD-21220 | biostudies-arrayexpress
Project description:In this study, miRNA expression in splenic lymphocytes from three genetically disparate lupus-prone mouse models (MRL-lpr, B6-lpr and NZB/WF1) were profiled. 49 miRNAs were found to be differentially expressed in MRL-lpr mice compared to MRL mice; and 24 miRNAs were differentially expressed in B6-lpr mice compared to B6 mice. Among these dysregulated miRNAs, we noted that 15 miRNAs were common to both lpr strains. Interestingly, microarray analysis of NZB/W and NZW at 3 months of age, an age when overt lupus disease is not evident in NZB/W mice, revealed that only one miRNA, miR-148a was significantly upregulated in NZB/W mice.
2011-12-17 | GSE22359 | GEO
Project description:In this study, miRNA expression in splenic lymphocytes from three genetically disparate lupus-prone mouse models (MRL-lpr, B6-lpr and NZB/WF1) were profiled. 49 miRNAs were found to be differentially expressed in MRL-lpr mice compared to MRL mice; and 24 miRNAs were differentially expressed in B6-lpr mice compared to B6 mice. Among these dysregulated miRNAs, we noted that 15 miRNAs were common to both lpr strains. Interestingly, microarray analysis of NZB/W and NZW at 3 months of age, an age when overt lupus disease is not evident in NZB/W mice, revealed that only one miRNA, miR-148a was significantly upregulated in NZB/W mice. The aim of this porject is to determine the common miRNA expression changes in splenocytes from different strains of murine lupus models. The splenocytes were prepared from genetically lupus-prone female mice including MRL/MpJ-Faslpr/J (MRL-lpr), NZBWF1/J (NZB/W), B6.MRL-Faslpr/J (B6-lpr) and their control mice MRL/MpJ (MRL), NZW/LacJ (NZW) and C57BL/6J (B6) mice (The Jackson laboratory, ME). Total RNAs, containing miRNAs were isolated from whole splenocytes using mirVana miRNA isolation kits (Ambion) following manufactory’s instructions and sent to LC Sciences (http://www.lcsciences.com/) for the microarray assay. The mouse miRNA array chips (Chip ID miRMouse 12.0 version), which included 617 unique, mature, mouse miRNA, based on the Sanger miRBase Release 12.0, were used in the assay.
2011-12-17 | E-GEOD-22359 | biostudies-arrayexpress
Project description:MRL/Faslpr mice is a lupus prone strain that exhibits lupus disease features at 12-16 weeks of age, including high-titer circulating anti-DNA antibodies, splenomegaly, lymphadnopathy, skin lesions, and IgG deposits in the kidney. At 16-24 weeks of age, CD4+ B220- CD44+ T cells were sorted into three populations based on the expression of two cell surface molecules, CD62L and PSGL1. CD62Lhi PSGL1hi, CD62Llo PSGL1hi, and CD62Llo PSGL1lo CD4+ T cells were isolated directly ex vivo. There was no treatment given to the animals. Naive (CD62Lhi CD44lo) CD4+ B220- T cells were isolated from young 6-8 week old female mice for comparison. We used a microarray to identify unique features of the CD62Llo PSGL1lo population in comparison to naïve CD4+ T cells and other activated CD4+ T cells. Cells were isolated from the spleens of aged (16-24 weeks) female MRL/Faslpr mice directy ex vivo, and immediatley sorted into 3 populations; CD62Lhi PSGL1hi, CD62Llo PSGL1hi, and CD62Llo PSGL1lo. All 3 populations of cells were previously gated on TCRb+, CD4+, B220-, CD44+. Naive CD4 T cells were isolated directly ex vivo from the spleens of young (6-8 weeks) female MRL/Faslpr mice, and immediately sorted by gating on TCRb+, CD4+, B220-, CD62Lhi, CD44lo. Three indepedent sorts were performed. RNA was isolated using Qiagen's RNAeasy kit and total RNA was submitted to the W.M. Keck Foundation Biotechnology Resource Laboratory at Yale for amplification and hybridization to Affymetrix Mouse Genome 430 2.0 GeneChips.
2010-03-18 | E-GEOD-20735 | biostudies-arrayexpress
Project description:MRL/Faslpr mice is a lupus prone strain that exhibits lupus disease features at 12-16 weeks of age, including high-titer circulating anti-DNA antibodies, splenomegaly, lymphadnopathy, skin lesions, and IgG deposits in the kidney. At 16-24 weeks of age, CD4+ B220- CD44+ T cells were sorted into three populations based on the expression of two cell surface molecules, CD62L and PSGL1. CD62Lhi PSGL1hi, CD62Llo PSGL1hi, and CD62Llo PSGL1lo CD4+ T cells were isolated directly ex vivo. There was no treatment given to the animals. Naive (CD62Lhi CD44lo) CD4+ B220- T cells were isolated from young 6-8 week old female mice for comparison. We used a microarray to identify unique features of the CD62Llo PSGL1lo population in comparison to naïve CD4+ T cells and other activated CD4+ T cells.
2010-03-18 | GSE20735 | GEO
Project description:Our previous study demonstrated a significant upregulation of a large set of miRNAs at the genomic imprinted Dlk1-Dio3 locus in lymphocytes of diverse murine lupus-prone strains. The upregulation of Dlk1-Dio3 miRNAs in lupus-prone mice is correlated with the global DNA hypomethylation. In this study, by performing genome-wide DNA methylation analysis, we reported that Dlk1-Dio3 genomic region in CD4+ T cells of MRL/lpr mice was hypomethylated, further linking hypomethylation to the increased expression of Dlk1-Dio3 miRNAs in lupus. Then, we assessed the gene expression levels of enzymes that either write (DNA methyltransferases, DNMTs) or erase DNA methylation (Ten-eleven translation proteins, TETs) to understand the molecular contributor to the DNA hypomethylation in MRL/lpr CD4+ T cells. The expression levels of Dnmt1, Dnmt3b, Tet1, and Tet2 were significantly increased in CD4+ T cells of MRL/lpr mice, as well as in B6/lpr and B6.sle123 mice, compared to their respective control mice. These data indicate the significant involvement of the TETs-mediated active demethylation pathway rather than reduced DNMTs-mediated passive demethylation pathway in the hypomethylation of murine lupus CD4+ T cells. The transcription factor, early growth response 2 (EGR2) is critically involved in regulating T cell functions and autoimmunity. In this research, we found that Egr2 deletion in B6/lpr mice notably reduced methylation-sensitive Dlk1-Dio3 cluster miRNAs expression in CD4+ T cells. Surprisingly, even though EGR2 has been shown to induce DNA demethylation by recruiting TET2, we found that deleting Egr2 in B6/lpr mice induced a higher number of hypomethylated DMRs than hypermethylated DMRs at either whole genome or the Dlk1-Dio3 locus in CD4+ T cells of B6/lpr mice. These data are the first finding on the positive role of EGR2 on the expression of Dlk1-Dio3 cluster miRNAs in lupus mice. Given that Dlk1-Dio3 miRNAs target the major signaling pathways in autoimmunity, these data provide a new perspective in understanding the potential pathogenic role of upregulated EGR2 in lupus.
2023-12-04 | GSE242955 | GEO
Project description:A total of 48 female MRL/lpr mice were included in this study and divided into six groups: JPZS group (Low, medium, and high doses), 5-aza-CdR group, and DC_517 group, with eight mice in each group. Eight female C57BL/6 mice were used as controls. The mice were subjected to the corresponding intervention measures for eight weeks. The impact of JPZS on the disease progression of MRL/lpr mice was evaluated using enzyme-linked immunosorbent assay (ELISA) and serum biochemical parameters. Moreover, immunofluorescence staining and flow cytometry were employed to investigate alterations in the proportions of Tregs and Th17 cells. CD4+ T cells were isolated from the spleen for subsequent investigation, including quantitative real-time PCR, western blotting, and determination of DNA methylation levels. Furthermore, the enzymatic activity of CD4+ T cell-specific DNA methyltransferases was quantified using an EpiQuik DNMT detection kit.The results indicate that JPZS significantly improved the disease development of MRL/lpr mice in a dose-dependent manner. Immunofluorescence staining and flow cytometry suggest that JPZS can increase the ratio of Treg/Th17. Research has found that Foxp3 is at a high methylation level in CD4+ T cells of the model group, and the transcription level of Foxp3 mRNA is downregulated; JPZS can downregulate Foxp3 methylation levels of CD4+ T cells in the model group. Further research has found that the level of Foxp3 methylation is closely related to Dnmt1 enzyme activity, and JPZS can downregulate Dnmt1 enzyme activity, thereby upregulating the transcription level of Foxp3 mRNA.
2025-05-31 | GSE296851 | 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, as well as their relevant mouse models such as MRL/lpr. We isolated the kidneys tissues pooled from six female MRL/lpr mice or from three control mice. Total RNA was extracted for the TaqManM-BM-. Low Density Assay v3.0
2012-12-19 | E-GEOD-37423 | biostudies-arrayexpress
Project description:Background: Bortezomib (Bz) is a proteasome inhibitor that directly targets antibody-producing plasma cells. We recently reported the first randomized control trial that evaluated the effects of Bz in patients with systemic lupus erythematosus (SLE). In that study, we demonstrated that Bz treatment is associated with many adverse reactions in patients with refractory disease. In the present study, we examine the therapeutic and toxic effects of Bz on MRL/MpJ-lpr/lpr (MRL/lpr) mice with severe disease activity. Methods: Female MRL/lpr mice at 10 and 14 weeks of age were treated with phosphate-buffered saline (PBS) (n = 13), Bz (750 μg/kg twice weekly) (n = 12), and cyclophosphamide (Cyc) (1 mg/body, once in 2 weeks) (n = 15). Cellular subsets, serum immunoglobulin, anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibody titer, and a pathological index of glomerulonephritis were then analyzed at 22 weeks of age. Survival curves of the 10 and 14 weeks-Bz-treated groups were compared. Blood counts, creatinine, liver enzymes, and serum cytokine levels were measured 1 week after Bz treatment. Gene expression profiling of spleens from Bz and Cyc treatment mice were compared with those from control mice. Results: The anti-dsDNA antibody levels were significantly higher in 14- than in 10-week-old mice, indicating a higher disease activity at 14 weeks. A significant decrease in the number of splenic cells and glomerulonephritis index was observed in Bz- and Cyc-treated mice. Bz, but not Cyc, significantly decreased serum immunoglobulin and anti-dsDNA antibody titer levels. Survival curve analysis revealed a significantly higher mortality rate in 14- than in 10-week-old Bz-treated and control groups. Following two injections of Bz, serum IL-6 and TNF-α levels were significantly more elevated in 14- than in 10-week-old mice. Potentially immunogenic molecules, such as heat shock proteins and calreticulin, were specifically upregulated in spleens of Bz- but not Cyc-treated mice. Conclusions: In spite of its therapeutic effect, Bz treatment had more toxic effects associated with increased pro-inflammatory cytokine levels in mice with a higher disease activity. Understanding the mechanism of the toxicity and developing preventive strategies against it is important for the safe clinical application of Bz in human SLE.
2017-02-10 | GSE94750 | GEO
Project description:To identify any differentially expressed miRNAs in the CD4+ T cells of lupus. 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 human lupus. By using high-throughput microRNA profiling analysis, we identified that two miRNAs (miR-21 and miR-148a) overexpressed in CD4+ T cells from both lupus patients and lupus-prone MRL/lpr mice,which promote cell hypomethylation by repressing DNA methyltransferase 1 (DNMT1) expression.
2010-07-07 | GSE21220 | GEO