Cancer resistance is a major cause for longevity of the naked mole-rat. Recent liver transcriptome analysis in this animal compared to wild-derived mice revealed higher expression of alpha2-macroglobulin (A2M) and cell adhesion molecules, which contribute to the naked mole-rat's cancer resistance. Notably, A2M is known to dramatically decrease with age in humans. We hypothesize that this might facilitate tumour development. Here we found that A2M modulates tumour cell adhesion, migration and growth by inhibition of tumour promoting signalling pathways, e.g. PI3K / AKT, SMAD and up-regulated PTEN via down-regulation of miR-21, in vitro and in tumour xenografts. A2M increases the expression of CD29 and CD44 but did not evoke EMT. Transcriptome analysis of A2M-treated tumour cells, xenografts and mouse liver demonstrated a multifaceted regulation of tumour promoting signalling pathways indicating a less tumorigenic environment mediated by A2M. By virtue of these multiple actions the naturally occurring A2M has strong potential as a novel therapeutic agent. Overall design: 11 samples: 5 treated with PBS, 6 treated with A2M
The anti-tumorigenic activity of A2M-A lesson from the naked mole-rat.
Specimen part, Cell line, Treatment, Subject
View SamplesThe anaerobic metabolism of the opportunistic pathogen Pseudomonas aeruginosa is important for growth and survival during persistent infections. The two Fnr-type transcription factors Anr and Dnr regulate different parts of the underlying network. Both are proposed to bind to a non-distinguishable DNA sequence named Anr box.
Anaerobic adaptation in Pseudomonas aeruginosa: definition of the Anr and Dnr regulons.
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View SamplesReduced oxygen availability during embryogenesis leads to intra-uterine growth restriction (IUGR), increasing the risk for hypertension, cardiovascular and chronic kidney disease (CKD) in adults. Although this association has long been recognized, underlying mechanisms still require extensive research.
Fetuin-A is a HIF target that safeguards tissue integrity during hypoxic stress.
Specimen part, Treatment
View SamplesSix patients with seasonal allergic rhinitis were challenged daily for 8 days with birch pollen extract. A mucosal biopsy was obtained from one nostril at basline (day 0) and from the other nostril after allergen challenge (day 9).
Rapid recruitment of CD14(+) monocytes in experimentally induced allergic rhinitis in human subjects.
Specimen part, Treatment, Subject
View SamplesHistidine-rich glycoprotein (HRG) is a 75 kDa heparin-binding plasma protein which has been implicated in regulation of tumor angiogenesis and growth. To exert some of its biological functions, HRG acts on macrophages.This study was performed to assess changes in gene expression in peritoneal macrophages treated with HRG using oligonucleotide microarrays
Genetic deficiency in plasma protein HRG enhances tumor growth and metastasis by exacerbating immune escape and vessel abnormalization.
Specimen part, Disease, Treatment, Time
View SamplesIllumina RNA sequencing to study DEGs between freshly isolated and emigrated skin T cells Overall design: skin T cell RNA profile of freshly isolated T cells and emigrated T cells under IL-2, IL-4, TGF-beta and IL-2, IL-15 cytokine condition
The cytokine environment influence on human skin-derived T cells.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Functions of BET proteins in erythroid gene expression.
Specimen part, Treatment
View SamplesThe transcription factor NF-E2-related factor 2 (Nrf2) induces cytoprotective genes, but has also been linked to the regulation of hepatic energy metabolism. In order to assess the pharmacological potential of hepatic Nrf2 activation in metabolic disease, Nrf2 was activated over 8 weeks in mice on Western diet using two different siRNAs against kelch-like ECH-associated protein 1 (Keap1), the inhibitory protein of Nrf2. Whole genome expression analysis followed by pathway analysis demonstrated that the suppression of Keap1 expression induced genes that are involved in anti-oxidative stress defense and biotransformation, pathways proving the activation of Nrf2 by the siRNAs against Keap1. The expression of neither fatty acid- nor carbohydrate-handling proteins was regulated by the suppression of Keap1. Metabolic profiling of the animals did also not show effects on plasma and hepatic lipids, energy expenditure or glucose tolerance by the activation of Nrf2. The data indicate that hepatic Nrf2 is not a major regulator of intermediary metabolism in mice.
Chronic Activation of Hepatic Nrf2 Has No Major Effect on Fatty Acid and Glucose Metabolism in Adult Mice.
Specimen part, Treatment
View SamplesRole of bromodomain and extra-terminal motif (BET) proteins in GATA1-null erythrolbasts (G1E) and in differentiation induced by activation of conditional GATA1 tested by addition of BET inhibitor JQ1 (250nM)
Functions of BET proteins in erythroid gene expression.
No sample metadata fields
View SamplesCytoplasmic DNA triggers the activation of the innate immune system. While downstream signaling components have been characterized, the DNA sensing components remain largely elusive. We performed a systematic proteomics screen for proteins that associate with DNA, traversed to a screen for IFN--induced transcripts. We identified DSIRE (DNA sensor for the IL-1 response, previously called AIM2) as a candidate cytoplasmic sensor. DSIRE showed a marked selectivity for double-stranded DNA. DSIRE can recruit the inflammasome adaptor ASC and gets redistributed to ASC speckles upon coexpression of ASC. RNAi-mediated reduction of DSIRE expression led to an impairment in IL-1 maturation. Reconstitution of unresponsive cells with DSIRE, ASC, caspase 1 and IL-1 showed that DSIRE is sufficient for inflammasome activation. Overall, our data strongly suggest that DSIRE is a cytoplasmic DNA sensor for the inflammasome.
An orthogonal proteomic-genomic screen identifies AIM2 as a cytoplasmic DNA sensor for the inflammasome.
No sample metadata fields
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