The influence of resveratrol on rheumatoid fibroblast-like synoviocytes based on a gene chip transcription analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: margherita breisach
PROVIDER: E-GEOD-31685 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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2014-02-06 | E-GEOD-54711 | biostudies-arrayexpress
Project description:As susceptibility to many adult disorders originates in utero, we here hypothesized that fetal sex influences gene expression in placental cells and produces functional differences in human placentas. We found that fetal sex differentially affects gene expression in a cell-phenotype dependent manner among all four placental cell-phenotypes studied: cytotrophoblasts, syncytiotrophoblasts, arterial endothelial cells and venous endothelial cells. The markedly enriched pathways in males were identified to be signaling pathways for graft-versus-host disease as well as the immune and inflammatory systems, both supporting the hypothesis that there is reduced maternal-fetal compatibility for male fetuses. Our study is the first microarray study investigating sexual dimorphism in purified and characterized somatic cells from a single human tissue, the placenta, that underlines the importance of considering fetal sex as an independent variable in any work using human placenta. Arterial and venous endothelial cells were isolated from eight different placentas, four of each sex. A total of ten placentas were used for isolation of cytotrophoblasts and six for syncytiotrophoblasts, with equal numbers from each sex.
2013-10-01 | E-GEOD-44368 | biostudies-arrayexpress
Project description:The aim of our study is to increase understanding of the antiproliferative and pro-apoptotic potency of resveratrol by identifying genes which underlie involved pathological pathways and biological process. Therefore, we performed a gene Chip Transcription Analysis with subsequent Protein ANalysis THrough Evolutionary Relationships (PANTHER) analysis to evaluate which transcripted genes are significantly influenced by resveratrol.
2013-07-31 | GSE31685 | GEO
Project description:The classical sacrococcygeal chordoma tumor presents with a typical morphology of lobulated myxoid tumor tissue with cords, strands and nests of tumor cells consisting of small non-vacuolated cells, intermediate cells with a wide range of vacuolization and large heavily vacuolated (physaliferous) cells. Because of its rare incidence, lack of suited model systems and technical limitations analysis was only performed on bulk tumor mass neglecting its heterogeneous composition. We aimed at elucidating the differences between small non-vacuolated and large physaliferous cells on the genomic and transcriptomic level. Secondly, we intended to clarify whether the observed cell types are derived from genetically distinct clones or rather represent different phenotypes. Using the chordoma cell line MUG-Chor1 we monitored morphological changes via time lapse experiments. We isolated pure fractions of each phenotype by means of laser microdissection or micromanipulation allowing phenotype-specific analysis. Pools of 100 cells each were genetically profiled after whole genome amplification by array comparative genomic hybridization. For expression analysis 20 cells each were subjected to whole transcriptom amplification, forwarded to RNA microarray analysis and qRT-PCR. Time lapse analysis unveiled small non-vacuolated cells to develop into large physaliferous cells via intermediate cells containing an increasing amount of vacuoles. Furthermore, we showed small and large physaliferous cells to proliferate at the same rate but intermediate cells to be the most proliferating cell phenotype. Small non-vacuolated and large physaliferous cells showed identical copy number variations. Despite their obvious morphological disparities we detected only modest changes in over all gene expression. However, verification of candidate genes yielded significant up-regulation of ALG11 (700-fold), PPP2CB (18.6-fold), and UCHL3 (18.7-fold) in large physaliferous cells. Of two different cell types (large and small MUG-Chor1 cells) we analysed each in triplicates. In total 6 cell pools were analysed.
2013-08-30 | E-GEOD-48779 | biostudies-arrayexpress
Project description:Inflammation-mediated oncogenesis has been implicated in a variety of cancer types. Rheumatoid synovial tissues can be viewed as a tumor-like mass, consisting of hyperplastic fibroblast-like synoviocytes (FLSs). FLSs of rheumatoid arthritis (RA) patients have pro-migratory and invasive characteristics, which may be caused by chronic exposure to genotoxic stimuli, including hypoxia and growth factors. We tested whether a transformed phenotype of RA-FLSs is associated with placental growth factor (PlGF), a representative angiogenic growth factor induced by hypoxia. Here, we identified PlGF-1 and PlGF-2 as the major PlGF isoforms in RA-FLSs. Global gene expression profiling revealed that cell proliferation, apoptosis, angiogenesis, and cell migration were mainly represented by differentially expressed genes in RA-FLSs transfected with siRNA for PlGF. Indeed, PlGF-deficient RA-FLSs showed a decrease in cell proliferation, migration, and invasion, but an increase in apoptotic death in vitro. PlGF gene overexpression resulted in the opposite effects. Moreover, exogeneous PlGF-1 and PlGF-2 increased survival, migration, and invasiveness of RA-FLSs by binding their receptors, Flt-1 and NP-1, up-regulating the expression of anti-apoptotic molecules, pErk and Bcl2. Knock-down of PlGF transcripts reduced RA-FLS proliferation in a xeno-transplantation model. Collectively, in addition to their role for neovascularization, PlGF-1 and -2 promote proliferation, survival, migration, and invasion of RA-FLSs in an autocrine and paracrine manner. These results demonstrated how primary cells of mesenchymal origin acquired an aggressive and transformed phenotype. PlGF and its receptors thus offer new targets for anti-FLS therapy. The FLSs were prepared from the synovial tissues of RA patients and incubated in DMEM supplemented with 10% FBS. Cells were cultured in RPMI supplemented with 10% FBS. There are 4 FLS samples treated with PlGF siRNA, and 4 FLS samples treated with control siRNA.
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Project description:Invasive pannus, mainly composed of fibroblast-like synoviocytes (FLSs), is a hallmark of rheumatoid arthritis (RA) pathology. Secreted proteins from RA-FLS play key roles in RA invasive pannus. However, RA-FLS-derived secretome associated with invasive pannus has not been systematically investigated. Here, we first identified 843 secreted proteins from RA-FLSs treated with TNFα and IL-1β using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Functional enrichment analysis revealed that 58.5% (493 proteins) of the secretome were associated with pannus-driven RA pathologies. Among them, parallel reaction monitoring (PRM) analysis then identified 16 secreted proteins that were increased in RA SFs (117 samples) than in OA SFs (45 samples). Of them, MYH9 further showed significant positive correlations with RA pathological parameters, such as synovial hyperplasia, increased articular vascularity, and inflammation severity. Molecular and cellular experiments confirmed that MYH9 was expressed in RA-FLSs and more highly under disease-aggravating conditions, and MYH9 depletion significantly defected migration and invasion of RA-FLS in RA pannus. Our study provides a comprehensive resource of RA-FLS-derived secretome, and our results suggest MYH9 that was increased in RA SF and strongly correlated with disease severity as a potential therapeutic target for invasive pannus.
2023-06-30 | PXD041077 | Pride
Project description:Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT, and TL1A. DcR3 was recently reported not only to act as a decoy receptor for these TNFRs but also to play a role as a ligand for the pathogenesis of RA. We hypothesized that DcR3 regulates the gene expression in RA-FLS. We used to search for genes in which expression in RA-FLS is regulated by the ligation of DcR3. RA-FLS were obtained from 4 RA patients (sample1-4). Each sample was incubated with control IgG1 or human DcR3-Fc. Gene expression in RA-FLS stimulated by DcR3-Fc was compared with that of their respective unstimulated controls.
2013-04-02 | E-GEOD-45665 | biostudies-arrayexpress
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