Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Alternatively Spliced Variants of Interleukin-4 Promote Inflammation Differentially

ABSTRACT: IL-4d2 is a natural splice variant of IL-4 which lacks the region encoded by the second exon. Numerous recent reports suggested that the expression levels of IL-4d2 change in various diseases, especially those with pulmonary involvement, but the effects of IL-4d2 on the lungs in vivo have never been studied. Replication-deficient adenovirus-mediated gene delivery of mouse IL-4d2 to mouse lungs in vivo was used, and the effects compared with similar adenoviral delivery of mouse IL-4 or with infection with a NULL viral construct. The objective was to determine whether full-length wild-type Interleukin-4 encoded by exons 1-4 (IL-4) and alternatively spliced variant econded by exons 1,3, and 4 (IL-4d2) differentially affect gene expression in the lungs in vivo. The results show that IL-4d2 and IL-4 affected global gene expression differentially. Keywords: Comparative analysis of gene delivery of alternative splice variants in vivo

ORGANISM(S): Mus musculus

PROVIDER: GSE23016 | GEO | 2011/03/07

SECONDARY ACCESSION(S): PRJNA131519

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Alternatively Spliced Variants of Interleukin-4 Promote Inflammation Differentially

Project description:IL-4d2 is a natural splice variant of IL-4 which lacks the region encoded by the second exon. Numerous recent reports suggested that the expression levels of IL-4d2 change in various diseases, especially those with pulmonary involvement, but the effects of IL-4d2 on the lungs in vivo have never been studied. Replication-deficient adenovirus-mediated gene delivery of mouse IL-4d2 to mouse lungs in vivo was used, and the effects compared with similar adenoviral delivery of mouse IL-4 or with infection with a NULL viral construct. The objective was to determine whether full-length wild-type Interleukin-4 encoded by exons 1-4 (IL-4) and alternatively spliced variant econded by exons 1,3, and 4 (IL-4d2) differentially affect gene expression in the lungs in vivo. The results show that IL-4d2 and IL-4 affected global gene expression differentially. Keywords: Comparative analysis of gene delivery of alternative splice variants in vivo There were three mice overexpressing mouse IL-4 in their lungs, three mice overexpressing mouse IL-4d2 in their lungs, and three mice similarly infected with control AdV-NULL virus not encoding a cytokine.

2011-03-07 | E-GEOD-23016 | biostudies-arrayexpress

Validation of alternatively spliced protein isoforms in human mesenchymal stem cells

Project description:Alternative splicing of mRNA diversifies the function of human proteins, with tissue- and cell-specific protein isoforms being the most difficult to validate. While transcriptomic experiments enable the detection of many alternatively spliced transcripts, it is not known if these transcripts have protein-coding potential. We recently published the PG Nexus pipeline, which facilitates high confidence validation of exons and exon-exon junctions of spliced transcripts by integrating transcriptomics and proteomics data. Using the PG Nexus, we analyzed undifferentiated human mesenchymal stem cells and compared the number of protein isoforms validated using different protein sequence database, including public online databases and RNA-seq derived databases. With significant overlaps with other databases, we identified 8,011 exons and 3,824 splice junctions with the Ensembl database. Both exonic and junction peptides were important for protein isoform validation. The Ensembl database consistently outperformed the other data sources, but predicted open reading frames from RNA-seq derived transcripts were comparable, with only 6 less splice junctions validated. Using proteotypic and isoform-specific peptides, we validated 462 protein isoforms. This number increases to 1,083 if multiple proteotypic peptides per protein are included. Multiplexing proteotypic peptides in SRM assays or similar experiments will increase the confidence and coverage of protein isoform validation experiments.

2015-05-20 | PXD001449 | Pride

Activation and Function of Alternatively and Classically Activated MH-S Alveolar Macrophages

Project description:Alveolar macrophages (AMs), the tissue dwelling monocytes of the lungs, are the first to encounter the menagerie of items that pass the mechanical barriers of the nose and throat. AMs must be able to mount an effective immune response against invading pathogens as well as maintain homeostasis in the lungs to avoid excessive inflammatory responses. In vivo data suggests that AMs can take on different phenotypes depending on the conditions of simulation. Limited progress has been made in defining the mechanisms responsible for these phenotypic issues largely due to logistical difficulties in isolating a sufficient number of cells from the lungs that have not been activated by the isolation protocol. To circumvent these logistical issues, an in vitro cell culture model was developed to study AM biology with specific emphasis on the generation of alternatively activated alveolar macrophages (AAAMs). Utilizing the BALB/c AM cell line MH-S it was determined that LPS could be used to generate classically activated AMs (CAAMs) and that IL-4 was effective in producing AAAMs. We examined the full transcriptome of AAAMs and CAAMs using microarray technology in an attempt to confirm previously described AAAM expression patterns and to identify new molecules associated with AM phenotypic change. AAAMs up-regulated an entirely distinct group of transcripts including genes encoding Arg1, Ym1 and a number of repair and remodeling genes whereas CAAMs up-regulated proinflammatory cytokines such as IL-1, IL-6 and IL-12. Additional novel markers are identified in this study to better characterize CAAMs and AAAMs in the lung. Keywords: Characterization of Cell Type Based on Activation Stimulus

2010-12-15 | GSE6785 | GEO

Microarray validation of an alternative splicing database

Project description:Alternative splicing generates functional diversity in higher organisms through alternative first and last exons, skipped and included exons, intron retentions and alternative donor and acceptor sites. In large-scale microarray studies in human and mouse, emphasis so far has been placed on exon-skip events, leaving the prevalence and importance of other splice types largely unexplored. Using a new human splice variant database and a genome-wide microarray to probes thousands of splice events of each type, we measured differential expression of splice types across 6 pairs of diverse cell lines and validated the database annotation process. Results suggest that splicing in human is more complex than simple exon skip events, which account for a minority of splicing differences. The relative frequency of differential expression of the splice types correlates with what is found by our annotation efforts. In conclusion, alternative splicing in human cells is considerably more complex than the canonical example of the exon-skip. The complementary approaches of genome-wide annotation of alternative splicing in human and design of genome-wide splicing microarrays to measure differential splicing in biological samples provide a powerful high-throughput tool to study the role of alternative splicing in human biology. Keywords: alternative splicing

2007-12-08 | GSE9734 | GEO

Whole Genome Exon Arrays Identify Differential Expression of Alternatively Spliced, Cancer-related Genes in Lung Cancer

Project description:Alternative processing of pre-mRNA transcripts is a major source of protein diversity in eukaryotes and has been implicated in several disease processes including cancer. In this study we have performed a genome wide analysis of alternative splicing events with the GeneChip Human Exon 1.0 ST Array from Affymetrix in lung adenocarcinoma. We found that ~13.3% of the 17800 core Refseq genes appear to have alternative transcripts that are differentially expressed in lung adenocarcinoma versus normal. According to their known functions the largest subset of these genes (30.8%) is believed to be cancer related. Detailed analysis was performed for several genes using PCR, quantitative RT-PCR and DNA sequencing. We found overexpression of ERG variant 2 but not variant 1 in lung tumors and overexpression of CEACAM1 variant 1 but not variant 2 in lung tumors but not in breast or colon tumors. We also identified a novel, overexpressed variant of CDH3 and verified the overexpression of a novel variant of P16. These findings demonstrate how analysis of alternative pre-mRNA processing can shed additional light on differences between tumors and normal tissues as well as between different tumor types. Such studies may lead to the development of additional tools for tumor diagnosis, prognosis and therapy. Keywords: Alternative splice analysis of exon data with ANOVA compared tumor and matched normal 20 tumor/normal paired specimens (n=40). Tumor samples are from lung adeno carcinoma whereas normals are from adjacent normal lung tissue.

2008-10-17 | E-GEOD-12236 | biostudies-arrayexpress

An alternatively spliced variant of METTL3 mediates tumor suppression in hepatocellular carcinoma

Project description:Many steps of post-transcriptional mRNA processing have shown crucial roles in the tumorigenesis and progression of cancers, such as the N6-methyladenosine (m6A) modification and alternative splicing. Up-regulation of METTL3, the catalytic core of the m6A methyltransferase complex, increases the m6A levels and results in significant effects on the progression of hepatocellular carcinoma (HCC). However, alternative splicing of METTL3 has not been fully investigated and functions of its splice variants remain unclear. Here, we first analyze online and our transcriptomic data and obtain 13 splice variants of METTL3 besides the canonical full-length METTL3-A in HCC cell lines and tissues. Validated by RT-qPCR, we find that METTL3-D, one of the splice variants expressing a truncated METTL3 protein, exhibits higher levels than the METTL3-A in normal human livers but lower levels in HCC tumor tissues and cell lines. Further functional assays demonstrate that expression of METTL3-D decreases the cellular m6A modification, inhibits the proliferation, migration and invasion of HCC cells, and is negatively associated with the malignancy of patient tumors, exhibiting an opposite function as the full-length METTL3-A does. Analyses of TCGA data also show that HCC patients with higher levels of METTL3-D have longer survivals. This study demonstrates that the METTL3-D splice variant is a tumor suppressor, and it could be used as a potential target for the therapy of HCC.

2022-05-01 | GSE189372 | GEO

Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of Amyotrophic Lateral Sclerosis

Project description:CNS-delivery of Interleukin 4 (IL-4) - via a lentiviral-mediated gene therapy strategy - skews microglia to proliferate, inducing these cells to adopt the phenotype of slowly proliferating cells. Transcriptome analysis revealed that IL-4-treated microglia express a broad number of genes normally encoded by embryonic microglia.

2018-02-16 | GSE103607 | GEO

Mutations primarily alter the inclusion of alternatively spliced exons

Project description:Systematic mutagenesis has revealed that synonymous, non-synonymous and intronic mutations frequently alter the inclusion levels of alternatively spliced exons, suggesting that altered splicing might be a common mechanism by which mutations cause disease. However, most exons expressed in any cell are highly-included in mature mRNAs. Here, by performing deep mutagenesis of highly-included exons and by analysing the association between sequence variation and exon inclusion across the genome, we report that mutations only very rarely alter the inclusion of highly-included exons. This is true for both exonic and intronic mutations as well as for perturbations in trans. Therefore, mutations that affect splicing are not evenly distributed across the genome but are focussed in and around alternatively spliced exons with intermediate inclusion levels. These results provide a resource for prioritising synonymous and other variants as disease-causing mutations.

2020-06-29 | GSE151942 | GEO

Transcription profiling of two human paediatric cancer cell lines to identify alternatively spliced variants of Ciz1

Project description:Ciz1 promotes initiation of mammalian DNA replication and is present within nuclear matrix associated DNA replication factories. Depletion of Ciz1 from normal and cancer cells restrains entry to S phase and inhibits cell proliferation. Several alternative splicing events with putative functional consequences have been identified and reported, but many more variants are predicted to exist based on publicly available mRNAs and expressed sequence tags. Here we report the development and validation of a custom exon and exon-junction microarray focused on the human Ciz1 gene, capable of reproducible detection of differential splice-variant expression. Using a pair of paediatric cancer cell lines and a pool of eight normal lines as reference, the array identified expected and novel Ciz1 splicing events. One novel variant (delta 8-12) that encodes a predicted protein lacking key functional sites, was validated by quantitative RT-PCR and found to be over-represented in a range of other cancer cell lines, and over half of a panel of primary lung tumours.

2009-11-01 | E-MEXP-2331 | biostudies-arrayexpress

Interleukin-22 immunotherapy modulates pulmonary gene expression evocative of enhanced tissue barrier and reduces bacterial systemic invasion during severe influenza

Project description:Severe bacterial (pneumococcal) infections are commonly associated with influenza and are significant contributors to the excess morbidity and mortality of influenza. Disruption of lung tissue integrity during influenza participates in bacterial pulmonary colonization and dissemination out of the lungs. Interleukin (IL)-22 has gained considerable interest in anti-inflammatory and anti-infection immunotherapy over the last decade. In the current study, we investigated the effect of exogenous IL-22 delivery on the outcome of bacterial superinfection post-influenza. Our data show that exogenous treatment of influenza-infected mice with recombinant IL-22 reduces bacterial dissemination out of the lungs but is without effect on pulmonary bacterial burden. We describe an IL-22 specific gene signature in the lung tissue of IAV-infected (and naÃ¯ve) mice that might explain the observed effects. Indeed, exogenous IL-22 modulates gene expression profile in a way suggesting a reinforcement of tissue integrity. Our results open the way to alternative approaches for limiting post-influenza bacterial superinfection, particularly systemic bacterial invasion.

2018-05-31 | E-MTAB-6044 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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