We report the effect of DKK1 treatment during culture on the length and transcriptome of embryos on day 15 of development, supporting the notion that changes early in development affect later stages of development. Overall design: Bovine embryos were produced in vitro and exposed to either 0 or 100 ng/ml DKK1 from day 5 to 7 of culture. Embryos were transferred on day 7 and recovered on day 15 for evaluation of length and transciptome
Dickkopf-related protein 1 is a progestomedin acting on the bovine embryo during the morula-to-blastocyst transition to program trophoblast elongation.
Treatment, Subject
View SamplesMEK5 is activated by shear stress in large vessel endothelial cells (ECs) and contributes to the suppression of pro-inflammatory changes in the arterial wall. We used microarray analyses of total RNA from MEK5/CA-transduced HDMECs compared to LacZ control-transduced HDMECs to identify distinct classes of several regulated genes, including KLF4, eNOS, and ICAM.
MEK5 is activated by shear stress, activates ERK5 and induces KLF4 to modulate TNF responses in human dermal microvascular endothelial cells.
Specimen part, Cell line
View SamplesBackground & Aims: Ursodeoxycholic acid (UDCA) attenuates chemical and colitis-induced colon carcinogenesis in animal models. We investigated its mechanism of action on normal intestinal cells, in which carcinogenesis- or inflammation-related alterations do not interfere with the result. Methods: Alterations of gene expression were identified in Affymetrix arrays in isolated colon epithelium of mice fed with a diet containing 0.4% UDCA and were confirmed in the normal rat intestinal cell line IEC-6 by RT-PCR. The effect of the insulin receptor substrate 1 (Irs-1) expression and of ERK phosphorylation on proliferation was investigated in vitro by flow cytometry, western blotting, siRNA-mediated gene suppression or by pharmacological inhibition of the kinase activity. The ERK1-effect on Irs-1 transcription was tested in a reporter system. Results: UDCA-treatment in vivo suppressed potential pro-proliferatory genes including Irs-1 and reduced cell proliferation by more than 30%. In vitro it neutralised the proliferatory signals of IGF-1 and EGF and slowed down the cell cycle. Irs-1 transcription was suppressed due to high ERK1 activation. Both Irs-1 suppression and the persistent high ERK activation inhibited proliferation. Conversely, the decrease of phosphorylation of ERK1 (but not ERK2) or of its expression partially abrogated the inhibitory effects of UDCA. Conclusions: UDCA inhibits proliferation of intestinal epithelial cells by acting upon IGF-1 and EGF pathways and targeting ERK1 and, consequently, Irs-1. The inhibition of these pathways adds a new dimension to the physiological and therapeutic action of UDCA and, since both pathways are activated in inflammation and cancer, suggests new applications of UDCA in chemoprevention and chemotherapy.
UDCA slows down intestinal cell proliferation by inducing high and sustained ERK phosphorylation.
Specimen part, Cell line
View SamplesMacrophages from RA synovial fluids were compared to primary human monocyte-derived macrophages.
Interferon-γ Represses M2 Gene Expression in Human Macrophages by Disassembling Enhancers Bound by the Transcription Factor MAF.
Specimen part, Disease stage, Subject
View SamplesOxaliplatin (oxPt) resistance in colorectal cancers (CRC) is a major medical problem, and predictive markers are urgently needed. Recently, miR-625-3p was reported as a promising predictive marker. Here, we have used in vitro models to show that miR-625-3p functionally induces oxPt resistance in CRC cells, and have identified signalling networks affected by miR-625-3p. The p38 MAPK activator MAP2K6 was shown to be a direct target of miR-625-3p, and, accordingly, was downregulated in patients not responding to oxPt therapy. miR-625-3p resistance could be reversed in CRC cells by anti-miR-625-3p treatment and by ectopic expression of a miR-625-3p insensitive MAP2K6 variant. In addition, by reducing p38 MAPK signalling using either siRNA technology, chemical inhibitors to p38 or by ectopic expression of dominant negative MAP2K6 protein we induced resistance to oxPt. Transcriptome, proteome and phosphoproteome profiles revealed inactivation of MAP2K6-p38 signalling as one likely mechanism a possible driving force behind of oxPt resistance. Our study shows that miR-625-3p induces oxPt resistance by abrogating MAP2K6-p38 regulated apoptosis and cell cycle control networks, and corroborates the predictive power of miR-625-3p
miR-625-3p regulates oxaliplatin resistance by targeting MAP2K6-p38 signalling in human colorectal adenocarcinoma cells.
Subject
View SamplesPentoxifylline attenuated hypertrophic scars by influencing the cell cycles Overall design: mRNA profiles of control hypertrophic scar fibroblasts and pentoxifylline treated cells were generated by deep sequencing, in triplicate, using Ion Proton.
The Akt/FoxO/p27<sup>Kip1</sup> axis contributes to the anti-proliferation of pentoxifylline in hypertrophic scars.
Specimen part, Treatment, Subject
View SamplesNOD2 is an intracellular receptor for the bacterial cell wall component muramyl dipeptide (MDP) and variants of NOD2 are associated with chronic inflammatory diseases of barrier organs e.g. Crohn disease, asthma and atopic eczema. It is known that activation of NOD2 induces a variety of inflammatory and antibacterial factors. The exact transcriptomal signatures that define the cellular programs downstream of NOD2 activation and the influence of the Crohn-associated variant L1007fsinsC are yet to be defined. To describe the MDP-induced activation program, we analyzed the transcriptomal reactions of isogenic HEK293 cells expressing NOD2wt or NOD2L1007fsinsC to stimulation with MDP. Importantly, a clear loss-of-function could be observed in the cells carrying the Crohn-associated variant L1007fsinsC, while the NOD2wt cells showed differential regulation of growth factors, chemokines and several antagonists of NF-B, e.g. TNFAIP3 (A20) and IER3.
Genome-wide expression profiling identifies an impairment of negative feedback signals in the Crohn's disease-associated NOD2 variant L1007fsinsC.
Cell line, Time
View SamplesThe response to the presence of the ncpBVDV-infected PI or TI fetus is expected to provide information on the impact of the PI fetus on the immune response of the dam
Persistent fetal infection with bovine viral diarrhea virus differentially affects maternal blood cell signal transduction pathways.
No sample metadata fields
View SamplesBoar taint (BT) is an offensive odour or taste observed in pork from a proportion of non-castrated male pigs. Surgical castration is effective in avoiding BT, but animal welfare issues have created an incentive for alternatives such as genomic selection. In order to find candidate biomarkers, gene expression profiles were analysed from tissues of non-castrated pigs grouped by their genetic merit of BT. Differential expression analysis revealed substantial changes with log-transformed fold changes of liver and testis from -3.39 to 2.96 and -7.51 to 3.53, respectively. Co-expression network analysis revealed one module with a correlation of -0.27 in liver and three modules with correlations of 0.31, -0.44 and -0.49 in testis. Differential expression and co-expression analysis revealed candidate biomarkers with varying biological functions: phase I (COQ3, COX6C, CYP2J2, CYP2B6, ACOX2) and phase II metabolism (GSTO1, GSR, FMO3) of skatole and androstenone in liver to steroidgenesis (HSD17B7, HSD17B8, CYP27A1), regulation of steroidgenesis (STARD10, CYB5R3) and GnRH signalling (MAPK3, MAP2K2, MAP3K2) in testis. Overrepresented pathways included “Ribosome”, “Protein export” and “Oxidative phosphorylation” in liver and “Steroid hormone biosynthesis” and “Gap junction” in testis. Future work should evaluate the biomarkers in large populations to ensure their usefulness in genomic selection programs. Overall design: Total RNA was extracted from liver and testis of 48 Danish Landrace pigs with low- medium and high genetic merit of boar taint and sequenced by Illumina HiSeq 2500.
Systems genomics study reveals expression quantitative trait loci, regulator genes and pathways associated with boar taint in pigs.
Specimen part, Subject
View SamplesSelected soil-borne rhizobacteria can trigger an induced systemic resistance (ISR) that is effective against a broad spectrum of pathogens. In Arabidopsis thaliana, the root-specific transcription factor MYB72 is required for the onset of ISR, but is also associated with plant survival under conditions of iron deficiency. Here we investigated the role of MYB72 in both processes. To identify MYB72 target genes, we analyzed the root transcriptomes of wild-type Col-0, mutant myb72, and complemented 35S:FLAG-MYB72/myb72 plants in response to ISR-inducing Pseudomonas fluorescens WCS417. Five WCS417-inducible genes were misregulated in myb72 and complemented in 35S:FLAG-MYB72/myb72. Amongst these, we uncovered -glucosidase BGLU42 as a novel component of the ISR signaling pathway. Overexpression of BGLU42 resulted in constitutive disease resistance, whereas bglu42 was defective in ISR. Furthermore, we found 195 genes to be constitutively upregulated in MYB72-overexpressing roots in the absence of WCS417. Many of these encode enzymes involved in the production of iron-mobilizing phenolic metabolites under conditions of iron deficiency. We provide evidence that BGLU42 is required for their release into the rhizosphere. Together, this work highlights a thus far unidentified link between the ability of beneficial rhizobacteria to stimulate systemic immunity and mechanisms induced by iron deficiency in host plants.
β-Glucosidase BGLU42 is a MYB72-dependent key regulator of rhizobacteria-induced systemic resistance and modulates iron deficiency responses in Arabidopsis roots.
Specimen part
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