Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

TNF-a-induced MEK/ERK-dependent regulation of Cartilage Matrix Genes

ABSTRACT: TNF-a is increased in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis. TNF-a activates MEK/ERK in chondrocytes; however the overall functional relevance of MEK/ERK to TNF-a-regulated gene expression in chondrocytes is unknown. Chondrocytes were treated with TNF-a with or without the MEK1/2 inhibitor U0126 for 24 h. Microarray analysis was used to identify genes regulated by TNF-a in a MEK1/2-dependent fashion. Keywords: compound, signalling response

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE14402 | GEO | 2009/01/14

SECONDARY ACCESSION(S): PRJNA111789

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcription profiling of rat chondrocytes were treated with TNF-a with or without the MEK1/2 inhibitor U0126 for 24 h to investigate TNF-a-induced MEK/ERK-dependent regulation of Cartilage Matrix Genes

Project description:TNF-a is increased in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis. TNF-a activates MEK/ERK in chondrocytes; however the overall functional relevance of MEK/ERK to TNF-a-regulated gene expression in chondrocytes is unknown. Chondrocytes were treated with TNF-a with or without the MEK1/2 inhibitor U0126 for 24 h. Microarray analysis was used to identify genes regulated by TNF-a in a MEK1/2-dependent fashion. Experiment Overall Design: Primary chondrocytes from the femoral condyles of neonatal rats were treated with DMSO (control sample), TNF-a, U0126 (selective MEK1/2 inhibitor) or TNF-a and U0126. Two biological replicates were collected for each treatment. Total RNA was collected and analyzed by Affymetrix Microarray.

2009-01-17 | E-GEOD-14402 | biostudies-arrayexpress

miRNA-transcriptome profiling of growth plate cartilage

Project description:Cartilage originates from mesenchymal cell condensations that differentiate into chondrocytes of transient growth plate cartilage or permanent cartilage of the articular joint surface and trachea. MicroRNAs fine-tune the activation of entire signaling networks and thereby modulate complex cellular responses, but so far only limited data are available on miRNAs that regulate cartilage development. Here we characterize an miRNA which promotes the biosynthesis of a key component in the RAF/MEK/ERK pathway in cartilage. Specifically, by transcriptome profiling we identified miR-322 to be upregulated during chondrocyte differentiation. Among the various miR-322 target genes in the RAF/MEK/ERK pathway, only Mek1 was identified as a regulated target in chondrocytes. Surprisingly, an increased concentration of miR-322 stabilizes Mek1-mRNA to arise protein levels and dampen ERK1/2 phosphorylation, while cartilage-specific inactivation in mice linked the loss of miR-322 to decreased MEK1 levels and increased RAF/MEK/ERK pathway activation. Such mice died perinatally due to tracheal growth restriction and respiratory failure. Hence, a single miRNA can stimulate the production of an inhibitory component of a central signaling pathway to impair cartilage development.

2017-10-03 | GSE98036 | GEO

PDGF-induced genes regulated by the PI3K and MEK/ERK signaling pathways

Project description:Human T98G glioblastoma cells were stimulated with platelet-derived growth factor (PDGF) and analyzed by DNA microarrays, which identified 74 immediate-early gene transcripts. Cells were then treated with inhibitors to identify subsets of genes that are targets of the phosphatidylinositol 3-kinase (PI3K) and MEK/ERK signaling pathways. Four groups of PDGF-induced genes were defined: independent of PI3K and MEK/ERK signaling, dependent on PI3K signaling, dependent on MEK/ERK signaling, and dependent on both pathways. Cells were grown in Minimal Essential Medium (Invitrogen) supplemented with fetal calf serum (10%). For growth factor/inhibitor treatments, cells were incubated in serum-free medium for 72 h, and either left unstimulated, or stimulated for 30 min with human PDGF-BB (50 ng/ml) (Sigma). U0126 (Cell Signaling Technology) and LY294002 (BioMol) were added 60 min prior to PDGF addition. Keywords: other

2004-03-13 | GSE1128 | GEO

Critical requirement of ERK/MAPK signaling in respiratory tract development

Project description:The mammalian genome contains two ERK/MAP kinase kinase genes, Mek1 and Mek2, which encode dual-specificity kinases responsible for ERK/MAP kinase activation. To define the function of ERK/MAPK signaling pathway in lung development, we performed tissue-specific deletions of Mek1 function in a Mek2 null background. Inactivation of both Mek genes in mesenchyme resulted in several phenotypes including giant omphalocele, skeletal defects, pulmonary hypoplasia, abnormal trachea patterning, and death at birth. Microarray analysis with RNA extracted from lungs of E15.5 Dermo1+/Cre, Mek1+/flox;Mek2-/-;Dermo1+/Cre and Mek1flox/flox;Mek2-/-;Dermo1+/Cre embryos was performed to evaluate the molecular impact of the loss of all Mek alleles in mesenchyme on lung development. . Total RNA was isolated from lungs of E15.5 Dermo1+/Cre embryos (control), from E15.5 Mek1+/flox;Mek2- /-;Dermo1+/Cre embryos (experimental) and from E15.5 Mek1flox/flox;Mek2-/-;Dermo1+/Cre embryos (experimental). Four specimens were analyzed per genotype.

2014-09-02 | E-GEOD-51643 | biostudies-arrayexpress

Critical requirement of ERK/MAPK signaling in respiratory tract development

2014-09-02 | GSE51643 | GEO

BRAF siRNA NHGRI_Liang_BRAF

Project description:BRAF, one of three RAF serine/threonine kinases (ARAF, BRAF and CRAF), plays a major role in the RAS-RAF-MEK-ERK mitogen-activated protein kinase (MAPK) signaling pathway, which mediates cellular responses to growth signals. Recently a high frequency (~60%-70%) of activating BRAF mutations (predominantly V600E) has been reported in malignant melanoma. In order to identify the downstream effects of BRAF signaling on melanoma cell growth and gene expression, cDNA microarray analysis was carried out following BRAF siRNA or MEK1/2 inhibitor (U0126) treatment. Keywords: time series, siRNA time series, siRNA, drug treatment

2013-07-07 | E-GEOD-5481 | biostudies-arrayexpress

Phosphorylation ratio of pT vs pY ERK in MEK phosphorylation reaction determined by mass spectrometry

Project description:The purpose of this experiment is to determine the phosphorylation ratio of pT vs pY ERK present in ERK phosphorylation reaction by activated MEK E203K or MEK WildType. Aliquots were collected at 3 minutes 15 seconds, the time at which the mono-phosphorylated ERK is at its maximal. To determine the ratio between pT and pY ERK, synthetic AQUA peptides corresponding to the pY- and the pT-phosphorylated ERK were spiked into the sample. The two peptides have identical mass but they can be umabiguguously distinguished by their elution times and fragmentation spectra.

2020-01-14 | PXD016580 | Pride

Expression profile of Ras, MEK and ERK inhibited 16HBE bronchial epithelial cells

Project description:To identify Ras, MEK and ERK target genes which regulate tight junction formation in 16HBE bronchial epithelial cells

2018-12-01 | GSE63229 | GEO

Constitutively activating MEK1 mutations drive treatment refractory histiocytic neoplasms but confer response to ERK inhibition

Project description:Histiocytic neoplasms are clonal disorders of the monocyte/macrophage lineage defined by mutations activating MAP kinase signaling, including BRAFV600E mutations in ~50% of patients, which confer robust responses to BRAF inhibition. More recently, the MEK inhibitor cobimetinib was FDA-approved for BRAFV600-wild-type histiocytosis patients. Here following genomic analysis of 500 pediatric and adult patients with diverse histiocytoses, the most common alteration following BRAFV600E was MEK1E102_I103 in-frame deletion. MEK1E102_I103del and related RAF-independent MEK mutants were associated with an aggressive multi-system clinical phenotype with worse progression-free survival with MEK inhibition as compared to patients with other classes of MEK1/2 mutations. Given that cancer-associated MEK1/2 mutations have not been modeled in vivo and the clinical importance of MEK1 mutations in histiocytoses, we generated MEK1E102_I103del conditional knock-in mice. Using three distinct hematopoietic Cre drivers, these mice developed a 100% penetrant, lethal disorder by 6 weeks of age with expansion of classical and non-classical monocytes, macrophages, and Cd11b+ conventional dendritic cells which infiltrated hematopoietic organs, liver, and skin. MEK1-mutant mice were sensitive to single-agent treatment with the oral ERK inhibitor ulixertinib. We consequently treated five MEK1E102_I103del-mutant patients with ulixertinib on prospective IRB-approved Single Patient Use Expanded Access protocols, four of whom had disease refractory to MEK inhibition. Four of five patients experienced objective clinical and/or radiological responses to ulixertinib. These data reveal the impact of oncogenic MEK kinase mutations in vivo, identify patients with likelihood of resistance to MEK inhibition, and nominate ERK inhibition as a therapeutic approach to overcome resistance to MEK inhibition in histiocytoses.

2024-09-03 | GSE268618 | GEO

Transcription profiling of mouse chondrocytes treated with MEK/ERK pathway inhibitors

Project description:Objectives: To identify similarities and differences in gene expression data in the MEK/ERK and PI3K pathways and to determine how histone modification affects these same pathways. Goal: To identify and functionally characterize novel targets of these signaling pathways in the context of chondrocyte differentiation. Experiment Overall Design: Cartilage derived from the hind limbs of CD1 mice staged at 15.5 days of embryonic development were dissected and plated in primary chondrocyte monolayer cultures. Cells were treated with MEK/ERK pathway inhibitors (SB202190 and UO126), a PI3K inhibitor (LY294002), a histone deacetylase inhibitor (Trichostatin A) and the vehicle control (DMSO) for 24 hours. Total RNA was isolated from these samples and hybridized to Affymetrix MOE 430 2.0 chips at the London Regional Genomics facility. Experiment Overall Design: A total of 15 genechips were analyzed between 4 treatments and the vehicle (DMSO) control. Three biological replicates per treatment were executed. Experiment Overall Design: Experiment Overall Design:

2009-05-11 | E-GEOD-15069 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data