Ontology highlight
ABSTRACT:
PROVIDER: PRJNA592055 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10572036.fastq.gz | Fastqsanger.gz | |||
| SRR10572037.fastq.gz | Fastqsanger.gz | |||
| SRR10572038.fastq.gz | Fastqsanger.gz | |||
| SRR10572039.fastq.gz | Fastqsanger.gz | |||
| SRR10572040.fastq.gz | Fastqsanger.gz |
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Project description:Mitogen-activated protein kinases (MAPKs) regulate cardiomyocyte growth and apoptosis in response to extracellular stimulation, but the downstream effectors that mediate their pathophysiological effects remain poorly understood. We determined the targets and role of p38 MAPK in the heart in vivo by using local adenovirus-mediated gene transfer of constitutively active upstream kinase mitogen-activated protein kinase kinase 3b (MKK3bE) and wild-type p38α in rats. DNA microarray analysis of animals with cardiac-specific overexpression of p38 MAPK revealed that 264 genes were upregulated more than 2-fold including multiple genes controlling cell division, cell signaling, inflammation, adhesion and transcription. Several previously unknown p38 target genes were found. Using gel mobility shift assays we identified several cardiac transcription factors that were directly activated by p38 MAPK. Finally, we determined the functional significance of the altered cardiac gene expression profile by histological analysis and echocardiographic measurements, which indicated that p38 MAPK overexpression induced gene expression results in cell proliferation, myocardial inflammation and fibrosis. In conclusion, we defined the novel target genes and transcription factors as well as the functional effects of p38 MAPK in the heart. Expression profiling of p38 MAPK overexpression identified cell cycle regulatory and inflammatory genes critical for pathological processes in the adult heart. Experiment Overall Design: Left ventricular gene expression profiles three days after MKK3bE + WT p38α gene transfer were compared with those of Lac Z âtreated animals by screening Affymetrix Rat Expression Set 230_2.0 Arrays (there are 5 samples in both group).
2009-04-25 | E-GEOD-3866 | biostudies-arrayexpress
Project description:Oxaliplatin(OXA) chemotherapy protocols are used in treatment of cancers like colorectal (CRC) and pancreatic cancer. OXA causes peripheral neuropathy which is considered treatment limiting factor. In recent studies, it shows that omeprazole(OME) has antioxidant effect and can inhibit organic cation transporter 2 (OCT2) in kidney. So OME can protect against peripheral neuropathy induced by OXA through oxidative stress . Also OME activates extracellular-signal-regulated kinase(ERK) / mitogen activated protein kinase ( MAPK) pathway, so improves demyelinating symptoms.
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Project description:Mitogen-activated protein kinases (MAPKs) regulate cardiomyocyte growth and apoptosis in response to extracellular stimulation, but the downstream effectors that mediate their pathophysiological effects remain poorly understood. We determined the targets and role of p38 MAPK in the heart in vivo by using local adenovirus-mediated gene transfer of constitutively active upstream kinase mitogen-activated protein kinase kinase 3b (MKK3bE) and wild-type p38α in rats. DNA microarray analysis of animals with cardiac-specific overexpression of p38 MAPK revealed that 264 genes were upregulated more than 2-fold including multiple genes controlling cell division, cell signaling, inflammation, adhesion and transcription. Several previously unknown p38 target genes were found. Using gel mobility shift assays we identified several cardiac transcription factors that were directly activated by p38 MAPK. Finally, we determined the functional significance of the altered cardiac gene expression profile by histological analysis and echocardiographic measurements, which indicated that p38 MAPK overexpression induced gene expression results in cell proliferation, myocardial inflammation and fibrosis. In conclusion, we defined the novel target genes and transcription factors as well as the functional effects of p38 MAPK in the heart. Expression profiling of p38 MAPK overexpression identified cell cycle regulatory and inflammatory genes critical for pathological processes in the adult heart. Keywords: Gene transfer
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Project description:Highly pathogenic avian influenza viruses (HPAIV) induce severe inflammation in poultry and men. There is still an ongoing threat that these viruses may acquire the capability to freely spread as novel pandemic virus strains that may cause major morbidity and mortality. One characteristic of HPAIV infections is the induction of a cytokine burst that strongly contributes to viral pathogenicity. It has been suggested, that this cytokine overexpression is an intrinsic feature of infected cells and involves hyperinduction of p38 mitogen activated protein kinase (MAPK). Here we investigate the role of MAPK p38 signaling in the antiviral response against HPAIV in mice as well as in endothelial cells, the latter a primary source for cytokines during systemic infections. Global gene expression profiling of HPAIV infected endothelial cells in the presence of the MAP kinase p38-specific inhibitor SB202190 revealed, that inhibition of MAPK p38 leads to reduced expression of interferon (IFN) and other cytokines after A/Thailand/1(KAN-1)/2004 (H5N1) and A/FPV/Bratislava/79 (H7N7) infection. Furthermore, the expression of interferon stimulated genes (ISGs) after treatment with IFN or conditioned media from HPAIV infected cells was decreased when the target cells were preincubated with SB202190. Finally, promoter analysis confirmed a direct impact of p38 MAPK on the IFN-enhanceosome and ISG-promoter activity. In vivo inhibition of MAP kinase p38 greatly diminishes virus induced cytokine expression concomitant with reduced viral titers, thereby protecting mice from lethal infection. These observations show, that MAPK p38 acts on two levels of the antiviral IFN response: Initially the kinase regulates IFN induction and at a later stage MAPK p38 controls IFN signaling and thereby expression of IFN-stimulated genes. Thus, inhibition of MAP kinase p38 may be an antiviral strategy that significantly protects mice from lethal influenza via suppression of overshooting cytokine expression. HUVEC were infected with FPV in the presence or absence of a p38 MAP kinase inhibitor
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Project description:Epidermal keratinocytes respond to extracellular influences by activating cytoplasmic signal transduction pathways that change the transcriptional profiles of affected cells. To define responses to two such pathways, p38 and ERK, we used SB203580 and PD98059 as specific inhibitors, and identified the regulated genes after 1, 4, 24 and 48 hrs, using Affymetrix’ Hu133Av2 microarrays. Additionally, we compared genes specifically regulated by p38 and ERKs with those regulated by JNK and by all three pathways simultaneously. We find that the p38 pathway induces the expression of extracellular matrix and proliferation-associated genes, while suppressing microtubule-associated genes; the ERK pathway induces the expression of nuclear envelope and mRNA splicing proteins, while suppressing steroid synthesis and mitochondrial energy production enzymes. Both pathways promote epidermal differentiation and induce feedback inactivation of MAPK signaling. c-FOS, SRY and N-Myc appear to be the principal targets of the p38 pathway, Elk-1 SAP1 and HLH2 of ERK, while FREAC-4, ARNT and USF are common to both. The results for the first time comprehensively define the genes regulated by the p38 and ERK pathways in epidermal keratinocytes and suggest a list of targets potentially useful in therapeutic interventions. Human epidermal keratinocytes are grown in Keratinocyte Serum-Free Medium (Gibco) supplemented with 0.05 mg/ml bovine pituitary extract, 2.5 ng/ml epidermal growth factor, 0.09 mM CalCl2 and 1% penicillin/streptomycin (KGM). They are switched to Keratinocyte Serum Free-Media (Gibco) supplemented only with 1% penicillin/streptomycin (KBM) 24 h prior to commencing experiments. A set is left as controls, others treated with 5 uM JNK inhibitor SP600125, 15 uM p38 inhibitor SB203580, or 50 um ERK inhibitor PD98059. Timecourse of treated and parellel control samples over a 48 hr period was performed.
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Project description:Highly pathogenic avian influenza viruses (HPAIV) induce severe inflammation in poultry and men. There is still an ongoing threat that these viruses may acquire the capability to freely spread as novel pandemic virus strains that may cause major morbidity and mortality. One characteristic of HPAIV infections is the induction of a cytokine burst that strongly contributes to viral pathogenicity. It has been suggested, that this cytokine overexpression is an intrinsic feature of infected cells and involves hyperinduction of p38 mitogen activated protein kinase (MAPK). Here we investigate the role of MAPK p38 signaling in the antiviral response against HPAIV in mice as well as in endothelial cells, the latter a primary source for cytokines during systemic infections. Global gene expression profiling of HPAIV infected endothelial cells in the presence of the MAP kinase p38-specific inhibitor SB202190 revealed, that inhibition of MAPK p38 leads to reduced expression of interferon (IFN) and other cytokines after A/Thailand/1(KAN-1)/2004 (H5N1) and A/FPV/Bratislava/79 (H7N7) infection. Furthermore, the expression of interferon stimulated genes (ISGs) after treatment with IFN or conditioned media from HPAIV infected cells was decreased when the target cells were preincubated with SB202190. Finally, promoter analysis confirmed a direct impact of p38 MAPK on the IFN-enhanceosome and ISG-promoter activity. In vivo inhibition of MAP kinase p38 greatly diminishes virus induced cytokine expression concomitant with reduced viral titers, thereby protecting mice from lethal infection. These observations show, that MAPK p38 acts on two levels of the antiviral IFN response: Initially the kinase regulates IFN induction and at a later stage MAPK p38 controls IFN signaling and thereby expression of IFN-stimulated genes. Thus, inhibition of MAP kinase p38 may be an antiviral strategy that significantly protects mice from lethal influenza via suppression of overshooting cytokine expression.
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