Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA275379 | ENA |
REPOSITORIES: ENA
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Project description:Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease involving primarily the synovial membranes and articular structures of multiple joints. A hallmark of RA is the pseudo-tumoral expansion of fibroblast-like synoviocytes (FLS), as these cells invade and finally destroy the joint structure. RA FLS have been therefore proposed as a therapeutic target. > TNF-related apoptosis-inducing ligand (TRAIL) has been described as a pro-apoptotic factor on malignant cells. The fact that fibroblasts-like-synoviocytes (FLS) in rheumatoid arthritis RA patients exhibit tumor like features led us to investigate the effect of TRAIL on ex-vivo RA FLS. We have previously described that TRAIL induces apoptosis only in a subset of RA FLS, but an induction of proliferation in the surviving cells. This observation corresponds to the pleiotropic effects of TRAIL observed on primary human tumor cells. We also observed that sensitivity to TRAIL-induced apoptosis varied in RA FLS from one patient to another, and was correlated with disease severity. We therefore screened for genes that were differentially expressed in RA FLS sensitive and resistant to TRAIL induced apoptosis in order to understand molecular factors making cells resistant or sensitive to TRAIL induced apoptosis.
2018-02-12 | GSE65908 | GEO
Project description:Identify HIP1 binding proteins implicated in regulation of invasive property of Rheumatoid Arthritis (RA) fibroblast-like synoviocytes (FLS) by using FLS cell line from arthritic DA (highly invasive) and R6 (minimally invasive) arthritis-protected congenic rats, which differ in amino-acid changing HIP1 SNPs.
2024-04-18 | PXD051384 | Pride
Project description:To investigate the impact of mTOR inhibiton on TNFalpha-activated rheumatoid arthritis fibbroblast-like synoviocytes (RA-FLS)
2018-03-15 | E-MTAB-6457 | biostudies-arrayexpress
Project description:To address the regulation of interferon-stimulated genes expression by VGLL3 in fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients, VGLL3 was overexpressed in RA-FLS via a lentiviral vector. After four days of transfection, VGLL3-overexpressed RA-FLS and vector-transfected RA-FLS were subjected to RNA sequencing.
2022-08-17 | GSE200030 | GEO
Project description:Platelet microparticles (PMPs) are closely related to the activity of rheumatoid arthritis, and promote the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). In order to identify the possible mechanisms of the promotion effect on migration and invasion of RA-FLS by PMP, we used microarray analysis to detect the gene expressions of RA-FLSs after treatment with PMPs.
2017-06-06 | GSE99681 | GEO
Project description:Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLS) and synovial macrophages (SM), are crucial for the progression of rheumatoid arthritis (RA). Particularly, FLS of RA patients (RA-FLS) exhibit invasive characteristics reminiscent of cancer cells, destroying cartilage and bone, although it remains unresolved how RA-FLS exhibit invasive phenotype. RA-FLS and SM originate differently from mesenchymal and myeloid cells, respectively, but share many pathologic functions. However, the molecular signatures and biological networks representing the distinct and shared features of the two cell types are unknown. Presently, we performed global transcriptome profiling of FLS and SM obtained from RA and osteoarthritis patients. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining invasiveness of RA-FLS and pro-inflammatory properties of RA synovial macrophages (RA-SM), respectively. Interestingly, under interleukin1β-stimulated condition, RA-FLS newly acquired pro-inflammatory signature mimicking RA-SM without losing invasive properties. We next reconstructed a network model that delineates the shared, RA-FLS-dominant (invasive), and RA-SM-dominant (inflammatory) processes. From the network model, we selected 13 genes, including POSTN and TWIST1, as novel regulator candidates responsible for FLS invasiveness. Of note, POSTN and TWIST1 expressions were elevated in independent RA-FLS and were further instigated by interleukin1β. In vitro functional assays demonstrated the requirement of POSTN and TWIST1 for migration and invasion of RA-FLS stimulated with interleukin1β. Taken together, our systems approach to rheumatoid synovitis provides a basis for identifying novel regulators responsible for pathological features of RA-FLS and RA-SM, demonstrating how a certain type of cells acquires functional redundancy under chronic inflammatory conditions. To identify molecular signatures of FLS and MLS in RA joints, we isolated FLS from synovial tissues of RA and osteoarthritis (OA) patients, obtained synovial macrophages from synovial fluid of RA patients, and differentiated control macrophages from peripheral blood of healthy subjects. Also, we stimulated FLS with IL1β, and then analyzed gene expression profiles of both IL1β-stimulated RA-FLS and OA-FLS
2014-01-09 | E-GEOD-49604 | biostudies-arrayexpress
Project description:Activated fibroblast-like synoviocytes (FLS) are drivers of synovitis and structural joint damage in rheumatoid arthritis (RA). Despite the use of disease-modifying drugs, only about 50% of RA patients reach remission in real-world settings. We used an unbiased approach to investigate the effects of standard-of-care methotrexate (MTX) and a Janus kinase inhibitor, tofacitinib (TOFA), on gene expression in RA-FLS, in order to identify untargeted disease mediators.
2024-10-04 | GSE266310 | GEO
Project description:Rheumatoid synoviocytes, which consist of fibroblast-like synoviocytes (FLS) and synovial macrophages (SM), are crucial for the progression of rheumatoid arthritis (RA). Particularly, FLS of RA patients (RA-FLS) exhibit invasive characteristics reminiscent of cancer cells, destroying cartilage and bone, although it remains unresolved how RA-FLS exhibit invasive phenotype. RA-FLS and SM originate differently from mesenchymal and myeloid cells, respectively, but share many pathologic functions. However, the molecular signatures and biological networks representing the distinct and shared features of the two cell types are unknown. Presently, we performed global transcriptome profiling of FLS and SM obtained from RA and osteoarthritis patients. By comparing the transcriptomes, we identified distinct molecular signatures and cellular processes defining invasiveness of RA-FLS and pro-inflammatory properties of RA synovial macrophages (RA-SM), respectively. Interestingly, under interleukin1β-stimulated condition, RA-FLS newly acquired pro-inflammatory signature mimicking RA-SM without losing invasive properties. We next reconstructed a network model that delineates the shared, RA-FLS-dominant (invasive), and RA-SM-dominant (inflammatory) processes. From the network model, we selected 13 genes, including POSTN and TWIST1, as novel regulator candidates responsible for FLS invasiveness. Of note, POSTN and TWIST1 expressions were elevated in independent RA-FLS and were further instigated by interleukin1β. In vitro functional assays demonstrated the requirement of POSTN and TWIST1 for migration and invasion of RA-FLS stimulated with interleukin1β. Taken together, our systems approach to rheumatoid synovitis provides a basis for identifying novel regulators responsible for pathological features of RA-FLS and RA-SM, demonstrating how a certain type of cells acquires functional redundancy under chronic inflammatory conditions.
2014-01-09 | GSE49604 | GEO
Project description:We report the effects of Hfol on TNF induction of inflammatory genes in wild type cells versus cells depleted of GCN2 RNA-seq analysis of primary rheumatoid arthritis fibroblast like synoviocytes (RA-FLS) treated with TNFa in the presence or absence of Halofuginone (HF).
2020-03-22 | GSE145204 | GEO
Project description:Objectives: Epigenetics can influence disease susceptibility and severity. While DNA methylation of individual genes has been explored in autoimmunity, no unbiased systematic analyses have been reported. Therefore, a genome-wide evaluation of DNA methylation loci in fibroblast-like synoviocytes (FLS) isolated from the site of disease in rheumatoid arthritis (RA) was performed. Methods: Genomic DNA was isolated from six RA and five osteoarthritis (OA) FLS lines and evaluated using the Illumina HumanMethylation450 chip. Cluster analysis of data was performed and corrected using Benjamini–Hochberg adjustment for multiple comparisons. Methylation was confirmed by pyrosequencing and gene expression was determined by qPCR. Pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes. Results: RA and control FLS segregated based on DNA methylation, with 1859 differentially methylated loci. Hypomethylated loci were identified in key genes relevant to RA, such as CHI3L1, CASP1, STAT3, MAP3K5, MEFV and WISP3. Hypermethylation was also observed, including TGFBR2 and FOXO1. Hypomethylation of individual genes was associated with increased gene expression. Grouped analysis identified 207 hypermethylated or hypomethylated genes with multiple differentially methylated loci, including COL1A1, MEFV and TNF. Hypomethylation was increased in multiple pathways related to cell migration, including focal adhesion, cell adhesion, transendothelial migration and extracellular matrix interactions. Confirmatory studies with OA and normal FLS also demonstrated segregation of RA from control FLS based on methylation pattern. Conclusions: Differentially methylated genes could alter FLS gene expression and contribute to the pathogenesis of RA. DNA methylation of critical genes suggests that RA FLS are imprinted and implicate epigenetic contributions to inflammatory arthritis. Fibroblast-like synoviocyte cell-lines from osteoarthritis (OA) and rheumatoid arthritis (RA) patients.
2013-04-25 | E-GEOD-46364 | biostudies-arrayexpress