Endothelin-1 (ET-1), an endothelium-derived vasoconstrictor peptide, plays a role in the pathophysiology of cardiovascular disease. Transgenic mice that overexpress human preproET-1 selectively in the endothelium (eET-1) exhibit endothelial dysfunction, hypertrophic remodeling and vascular inflammation of resistance-size arteries in the absence of blood pressure elevation. To understand the mechanisms whereby ET-1 induces vascular damage, vascular gene expression using DNA microarrays was employed. RNA from mesenteric arteries of female and male young (6-7 weeks) and mature (6-8 months) eET-1 and wild type (WT) mice was isolated and changes in gene expression were determined by genome-wide expression profiling using Illumina microarray. This study revealed a set of genes potentially regulated by ET-1, which might be implicated in ET-1 induced-vascular damage.
Vascular gene expression in mice overexpressing human endothelin-1 targeted to the endothelium.
Sex, Age, Specimen part
View SamplesComparative RNA profiling between tumor cells and their secreted extracellular vesicles. Results revealed enrichment in genes involved in cellular migration and metastasis in extracellular vesicles, in agreement with their role as mediators of tumor progression.
In Vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior.
Cell line
View SamplesMicrogravity as well as chronic muscle disuse are two causes of low back pain originated at least in part from paraspinal muscle deconditioning. At present no study investigated the complexity of the molecular changes in human or mouse paraspinal muscles exposed to microgravity. The aim of this study was to evaluate longissimus dorsi and tongue (as a new potential in-flight negative control) adaptation to microgravity at global gene expression level. C57BL/N6 male mice were flown aboard the BION-M1 biosatellite for 30 days (BF) or housed in a replicate flight habitat on ground (BG). . Global gene expression analysis identified 89 transcripts differentially regulated in longissimus dorsi of BF vs. BG mice (False Discovery Rrate < 0,05 and fold change < -2 and > +2), while only a small number of genes were found differentially regulated in tongue muscle ( BF vs. BG = 27 genes).
Microgravity-Induced Transcriptome Adaptation in Mouse Paraspinal <i>longissimus dorsi</i> Muscle Highlights Insulin Resistance-Linked Genes.
Specimen part
View SamplesMicrogravity exposure as well as chronic muscle disuse are two of the main causes of physiological adaptive skeletal muscle atrophy in humans and murine animals in physiological condition. The aim of this study was to investigate, at both morphological and global gene expression level, skeletal muscle adaptation to microgravity in mouse soleus and extensor digitorum longus (EDL). Adult male mice C57BL/N6 were flown aboard the BION-M1 biosatellite for 30 days on orbit (BF) or housed in a replicate flight habitat on Earth (BG) as reference flight control.
Gene Expression Profiling in Slow-Type Calf Soleus Muscle of 30 Days Space-Flown Mice.
Sex, Specimen part
View SamplesEpithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) facilitate breast cancer (BC) metastasis, however stable molecular changes that result as a consequence of these processes remain poorly defined. Therefore, we sought to identify molecular markers that could distinguish tumor cells that had completed the EMT:MET cycle in the hopes of identifying and targeting unique aspects of metastatic tumor outgrowth.Therefore, normal murine mammary gland (NMumG) cells transformed by overexpression of EGFR (NME) cells were cultured in the presence of TGF-beta1 (5 ng/ml) for 4 weeks, at which point TGF-beta1 supplementation was discontinued and the cells were allowed to recover for an additional 4 weeks (Post-TGF-Rec). Total RNA was prepared from unstimulated cells (Pre-TGF) of similar passage and compared by microarray analysis.
Fibroblast growth factor receptor splice variants are stable markers of oncogenic transforming growth factor β1 signaling in metastatic breast cancers.
Specimen part
View SamplesThe protease activity of the paracaspase MALT1 plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor NF-kB and is thus essential for the expression of inflammatory target genes.
MALT1 Protease Activity Controls the Expression of Inflammatory Genes in Keratinocytes upon Zymosan Stimulation.
Treatment
View SamplesWe utilized oligonucleotide microarrays to measure cellular mRNA decay rates in mock- or reovirus-infected murine L929 cells to determine if changes in host mRNA expression are a consequence of reovirus-induced alterations in cellular mRNA stability.
Reovirus infection induces stabilization and up-regulation of cellular transcripts that encode regulators of TGF-β signaling.
Cell line, Time
View SamplesBackground and Aims: Recent identification of intracellular DNA sensing pathways and involvement in numerous diverse disease processes including viral pathogenesis and autoimmunity suggests a role for these processes in liver pathology. The presence of these pathways in the liver and their role in HBV infection is unknown. Methods: In order to characterize the role of DNA sensing pathways in the liver, we utilized in vitro models. Microarray was performed on DNA treated and HBV infected hepatoma primary human hepatocytes. Results: Here we show that HBV infection and foreign DNA results in a significant innate immune response characterized by the production of inflammatory chemokines.
Hepatitis B Virus and DNA Stimulation Trigger a Rapid Innate Immune Response through NF-κB.
Specimen part, Treatment
View SamplesThe pesticide rotenone, a neurotoxin that inhibits the mitochondrial complex I, and destabilizes microtubules (MT) has been linked to Parkinson disease (PD) etiology and is often used to model this neurodegenerative disease (ND). Many of the mechanisms of action of rotenone are posited mechanisms of neurodegeneration; however, they are not fully understood. Therefore, the study of rotenone-affected functional pathways is pertinent to the understanding of NDs pathogenesis. This report describes the transcriptome analysis of a neuroblastoma (NB) cell line chronically exposed to marginally toxic and moderately toxic doses of rotenone. The results revealed a complex pleiotropic response to rotenone that impacts a variety of cellular events, including cell cycle, DNA damage response, proliferation, differentiation, senescence and cell death, which could lead to survival or neurodegeneration depending on the dose and time of exposure and cell phenotype. The response encompasses an array of physiological pathways, modulated by transcriptional and epigenetic regulatory networks, likely activated by homeostatic alterations. Pathways that incorporate the contribution of MT destabilization to rotenone toxicity are suggested to explain complex I-independent rotenone-induced alterations of metabolism and redox homeostasis. The postulated mechanisms involve the blockage of mitochondrial voltage-dependent anions channels (VDACs) by tubulin, which coupled with other rotenone-induced organelle dysfunctions may underlie many presumed neurodegeneration mechanisms associated with pathophysiological aspects of various NDs including PD, AD and their variant forms. Thus, further investigation of such pathways may help identify novel therapeutic paths for these NDs.
Transcriptome analysis of a rotenone model of parkinsonism reveals complex I-tied and -untied toxicity mechanisms common to neurodegenerative diseases.
Cell line, Treatment, Time
View SamplesWNT-induced secreted protein 1 (WISP1/CCN4), a member of the CCN protein family, acts as a downstream factor of the canonical WNT-signaling pathway. A dysregulated expression of WISP1 often reflects its oncogenic potential by inhibition of apoptosis, a necessary form of cell death that protect cell populations for transformation into malignant phenotypes. WISP1-signaling is also known to affect proliferation and differentiation of human mesenchymal stem cells (hMSCs), which are fundamental for the constitution and maintenance of the musculoskeletal system. Our study emphasizes the importance of WISP1-signaling for cell survival of primary human cells. Therefore, we established a successful down-regulation of endogenous WISP1 transcripts through gene silencing in hMSCs. We were able to demonstrate the consequence of cell death immediately after WISP1 down-regulation took place. Bioinformatical analyses of subsequent performed microarrays from WISP1 down-regulated vs. control samples confirmed this observation. We uncovered several clusters of differential expressed genes important for cellular apoptosis induction and immuno-regulatory processes, thereby indicating TRAIL-induced and p53-mediated apoptosis as well as IFNbeta-signaling. Since all of them act as potent inhibitors for malignant cell growth, in vitro knowledge about the connection with WISP1-signaling could help to find new therapeutic approaches concerning cancerogenesis and tumor growth in musculoskeletal tissues.
WISP 1 is an important survival factor in human mesenchymal stromal cells.
Specimen part, Treatment
View Samples