Dual specificity phosphate 1 (DUSP1) has a key non-invasive predictive marker in preeclampsia
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE262147 | GEO | 2024/03/26
REPOSITORIES: GEO
Similar Datasets
Project description:Activation of the Mitogen activated protein kinase (MAPK) cascade following Toll-like receptor (TLR) stimulation enables innate immune cells to rapidly activate cytokine gene expression. A balanced response to signals of infectious danger requires that cellular activation is transient. Here, we identify the MAPK phosphatase Dual specificity phosphatase-1 (DUSP1) as an essential endogenous regulator of the inflammatory response to LPS. DUSP1-deficient (DUSP1-/-) bone marrow derived macrophages showed selectively prolonged activation of p38 MAPK and increased cytokine production. Intraperitoneal challenge of DUSP1-/- mice with LPS caused increased lethality and overshooting production of IL-6 and TNF?. Transcriptional profiling revealed that DUSP1 controls a significant fraction of LPS-induced genes, that includes IL-6 and IL-10 as well as the chemokines CCL3, CCL4 and CXCL2. In contrast, the expression of the important mediators of endotoxin lethality, IFN? and IL-12, was not significantly altered by the absence of DUSP1. These data together demonstrate a specific regulatory role of DUSP1 in controlling a subset of LPS-induced genes that determines the outcome of endotoxin shock. Keywords: in vivo analysis of splenic mRNA expression
2005-12-15 | GSE3565 | GEO
Project description:Adolescent cocaine abuse increases the risk for developing addiction in later life, but the underlying molecular mechanism remains poorly understood. Here, we establish adolescent cocaine-exposed (ACE) male mouse models. A subthreshold dose of cocaine (sdC) treatment, insufficient to produce conditioned place preference (CPP) in adolescent mice, induces CPP in ACE mice during adulthood, along with more activated CaMKII-positive neurons, higher dual specificity protein kinase phosphatase-1 (Dusp1) mRNA, lower DUSP1 activity, and lower DUSP1 expression in CaMKII-positive neurons in the medial prefrontal cortex (mPFC). Overexpressing DUSP1 in CaMKII-positive neurons suppresses neuron activity and blocks sdC-induced CPP in ACE mice during adulthood. On the contrary, depleting DUSP1 in CaMKII-positive neurons activates more neurons and further enhances sdC-induced behavior in ACE mice during adulthood. Also, ERK1/2 might be a downstream signal of DUSP1 in the process. Our findings reveal a role of mPFC DUSP1 in ACE-induced higher sensitivity to the drug in adult mice. DUSP1 might be a potential pharmacological target to predict or treat the susceptibility to addictive drugs caused by adolescent substance use.
2023-05-20 | GSE231074 | GEO
Project description:DUSP1 is involved in different cellular pathways including cancer cell proliferation, angiogenesis, invasion and resistance to chemotherapy. To understand more about the cellular responses regulated by DUSP1 in NSCLC cells, we interfered DUSP1 expression in the NSCLC cell line H460 and studied the changes in gene expression differentially regulated by this phosphatase. Keywords: Expression profiling by array in cells with genetic modification The human non small lung cancer cell line H460 used in this study was from ATCC (American Type Culture Collection). The cell line was maintained in RPMI (Gibco, Invitrogen) supplemented with 10% bovine serum and transfected by Lipofectamine Plus Reagent from Life Technologies as directed by the manufacturer. The DUSP1 pSuperRetro-derived vectors were constructed as described (Chattoppadhyay et al., 2006). Clones expressing siRNA for DUSP1 were selected for their ability to grow in the presence of puromycin and kept for selection. Stable transfection was confirmed by Western blotting. RNA was extracted and quality control was checked before hybridization on Affymetrix microarrays.
2010-12-09 | E-GEOD-19592 | biostudies-arrayexpress
Project description:DUSP1 is involved in different cellular pathways including cancer cell proliferation, angiogenesis, invasion and resistance to chemotherapy. To understand more about the cellular responses regulated by DUSP1 in NSCLC cells, we interfered DUSP1 expression in the NSCLC cell line H460 and studied the changes in gene expression differentially regulated by this phosphatase. Keywords: Expression profiling by array in cells with genetic modification
2010-12-09 | GSE19592 | GEO
Project description:Activation of the Mitogen activated protein kinase (MAPK) cascade following Toll-like receptor (TLR) stimulation enables innate immune cells to rapidly activate cytokine gene expression. A balanced response to signals of infectious danger requires that cellular activation is transient. Here, we identify the MAPK phosphatase Dual specificity phosphatase-1 (DUSP1) as an essential endogenous regulator of the inflammatory response to LPS. DUSP1-deficient (DUSP1-/-) bone marrow derived macrophages showed selectively prolonged activation of p38 MAPK and increased cytokine production. Intraperitoneal challenge of DUSP1-/- mice with LPS caused increased lethality and overshooting production of IL-6 and TNF. Transcriptional profiling revealed that DUSP1 controls a significant fraction of LPS-induced genes, that includes IL-6 and IL-10 as well as the chemokines CCL3, CCL4 and CXCL2. In contrast, the expression of the important mediators of endotoxin lethality, IFN? and IL-12, was not significantly altered by the absence of DUSP1. These data together demonstrate a specific regulatory role of DUSP1 in controlling a subset of LPS-induced genes that determines the outcome of endotoxin shock. Experiment Overall Design: Mice were injected intraperitoneally with E. coli LPS (10µg/g bodyweight) and sacrificed 6h later. Total spleen RNA (5 µg) was prepared, labeled and hybridized to Affymetrix MOE430A 2.0 GeneChips according to the manufacturer's instructions. Three biological replicates per condition were analysed. CEL Files were processed for global normalization and generation of expression values using the rma algorithm in the R affy package (www.bioconductor.org).
2007-11-01 | E-GEOD-3565 | biostudies-arrayexpress
Project description:DUSP1 is involved in different cellular pathways including cancer cell proliferation, angiogenesis, invasion and resistance to chemotherapy. To gain insight into the cellular signaling pathways involving DUSP1 actions and the response to Cisplatin (CDDP) in non small cell lung cancer (NSCLC), we have used a double strategy that combines microarray and SiRNA technology. This strategy provided a differential expression profile of genes involved in CDDP response in NSCLC cell line regulated by DUSP1 using H460 and H460cri and a time course to CDDP. KEYWORDS: Expression profiling by array in cells with genetic modification in response to CCDP treatment The human non small lung cancer cell line H460 used in this study was from ATCC (American Type Culture Collection). The cell line was maintained in RPMI (Gibco, Invitrogen) supplemented with 10% bovine serum and transfected by Lipofectamine Plus Reagent from Life Technologies as directed by the manufacturer. The DUSP1 pSuperRetro-derived vectors were constructed as described (Chattoppadhyay et al., 2006). Clones expressing siRNA for DUSP1 were selected for their ability to grow in the presence of puromycin and kept for selection. Stable transfection was confirmed by Western blotting. We analyzed the differences in expression of 47000 genes in H460 cells expressing DUSP1SiRNA (H460cri) compared with the parental cell line H460pSuperRetro vector (H460v) after 0, 1, 3 and 6 hours of CDDP exposure, in order to know the different pathways that were activated by CDDP treatment dependent on expression of DUSP1. RNA was extracted and quality control was checked before hybridization on Affymetrix microarrays.
2012-01-01 | E-GEOD-26704 | biostudies-arrayexpress
Project description:Background: Preeclampsia (PE) is a placental disease characterized by hypertension and proteinuria in pregnant women, which is associated with a high maternal and infantile morbidity. However, circulating biomarkers able to predict the prognosis of PE are lacking. Methods: Thirty-eight women were included in the study. They consisted of 19 patients with PE (13 with severe PE and 6 women with non-severe PE) and 19 gestational age-matched normal pregnancy controls. We measured coagulation pathway, endothelial responses and microparticle release and circulating gene expression in PE patient groups and normotensive controls. Results: The measurement of markers associated with coagulation pathway, endothelial activation and circulating microparticles enabled to discriminate PE from normal pregnancy but were not sufficient to distinguish severe from non-severe PE. PE patients also exhibited a specific transcriptional program distinct from that of control women and subtle differences were observed between severe and non-severe PE. Functional annotation of the up-modulated signature in PE highlighted two main functions related to ribosome and complement. Importantly, we found that 8 genes were specifically up-modulated in severe preeclampsia. Among these genes, the expression of VSIG4 was significantly increased in patients with severe preeclampsia in comparison with controls and patients with non-severe preeclampsia. Conclusion: Using transcriptional signatures of blood samples, we identified the gene encoding the estrogen receptor as a potential diagnostic marker of severe preeclampsia. In addition, the determination of this gene may improve the prognostic assessment of severe preeclampsia. Thirty-eight women were included in the study: 19 patients with PE, including 6 women with non-severe PE and 13 with severe PE, and 19 women with normal pregnancy (NP) selected according to age, weight, smoking status, race, gestational age at the inclusion, and blood pH (Table 1 of manuscript). Women with NP had no history of medical illness or medication, and received routing prenatal care. The diagnostic of PE was based on a blood pressure of M-bM-^IM-% 140/90 mmHg taken twice, uricemia above normal laboratory range (120-420 M-BM-5mol/L), and proteinuria higher than 300 mg in a 24 hour-collection, occurring after 20 gestational weeks in previously normotensive women (Table 2). The criteria used to define severe PE included one of the following conditions: a blood pressure higher than 160/110 mmHg, a proteinuria higher than 1500 mg/24h), a multisystem disorder, maternal cerebral symptoms (seizures, stroke) or intrauterine growth restriction below the 3M-BM-0 percentile. Women with multiple gestations, fetal congenital malformations/chromosomal abnormalities, recent infection, antiphospholipid antibodies, trauma, drug or alcohol abuse during pregnancy, preexisting hypertension, thrombophilia with PE history, or women receiving anticoagulant or antiaggregation therapy were excluded from the study. Two microarrays (one non-severe PE and one normal) were discarded from the analysis for technical reasons. Thus, only 36 microarrays are included here.
2014-05-14 | E-GEOD-48424 | biostudies-arrayexpress
Project description:Stress-activated protein kinases (SAPK) have been associated with sensorineural hearing loss (SNHL) of multiple etiologies. The activity of these kinases is tightly regulated by the dual-specificity phosphatase 1 (DUSP1), thus, DUSP1 loss of function leads to the sustained activation of SAPK. In the hearing organ, DUSP1 is an indispensable component of the stress response machinery, and its deficit accelerates SNHL progression, triggers the inflammatory response and promotes hair cell (HC) and spiral neurons (SGN) death. Here, we have studied the link between inflammation and redox imbalance in the cochlea by further characterizing the transcriptome of the Dusp1-/- mouse. RNAseq and subsequent GSEA indicated that Dusp1-/- mice present a distinct gene expression pattern of key cellular programs, including altered expression of genes of the inflammatory response and glutathione metabolism. To dissociate both components, Dusp1-/- mice were treated with the antioxidant N-acetylcysteine (NAC). Treatment with NAC delayed the onset of SNHL and reduced cochlear damage. Less HC were TUNEL+ and SGN showed less p-H2AX foci. NAC treatment not only improved redox balance but also reduced cytokine production and macrophage recruitment in Dusp1-/ -mice. In conclusion, our data point to DUSP1 as an essential node to control the cross-regulation of oxidative stress and inflammation.
2021-06-29 | GSE176114 | GEO
Project description:Preeclampsia (PE) is a major health problem in pregnancy, and miRNAs play a role in the pathophysiology of PE. However, the expression of circulating miRNAs was not analyzed in the second trimester of pregnancy, a period of major relevance to identify predictive biomarkers for PE. Therefore, we examined the expression profiles of 84 circulating miRNAs using PCR-array in plasma collected between 20 and 25 weeks of gestation from pregnant who subsequently developed PE and from those who remained healthy along pregnancy randomly selected from a prospective cohort of pregnant. miR-204-5p (P=0.0082) and other 22 miRNAs were upregulated (fold change > 2.0, while miR-24-3p, miR-22-3p, miR-143-3p, and miR-376c-3p had fold change > 4.0) and six miRNAs were downregulated (fold change < 0.5) in plasma from pregnant who developed PE. Target genes for differentially expressed miRNAs were extracted from the miRTarBase of experimentally validated miRNA-target interactions and used in gene set functional enrichment and REACTOME pathway analysis. The 20 pathways with the lowest false discovery rate for the upregulated and downregulated miRNAs are related to pathophysiology of PE, such as apoptosis, angiogenesis, and signal transduction, including signaling by receptor tyrosine kinases, VEGF and TGFB family members. Moreover, we explored the 37 target genes and pathways for miR-204-5p, including MMP-9, MALAT1, TGFBR2, and SIRT1. The circulating miRNAs differentially expressed in the second trimester of pregnancy are related to target genes and pathways of pathophysiological relevance during the early development of PE, and our findings provide for potential circulating predictive biomarkers in PE. For the PCR array, total RNA isolated was converted into cDNA using the miScript II RT Kit (Qiagen®, Leusden, Netherlands), according to the manufacturer’s instructions
2021-03-15 | GSE168860 | GEO
Project description:DUSP1 is involved in different cellular pathways including cancer cell proliferation, angiogenesis, invasion and resistance to chemotherapy. To gain insight into the cellular signaling pathways involving DUSP1 actions and the response to Cisplatin (CDDP) in non small cell lung cancer (NSCLC), we have used a double strategy that combines microarray and SiRNA technology. This strategy provided a differential expression profile of genes involved in CDDP response in NSCLC cell line regulated by DUSP1 using H460 and H460cri and a time course to CDDP. KEYWORDS: Expression profiling by array in cells with genetic modification in response to CCDP treatment
2012-01-01 | GSE26704 | GEO