Similar Datasets
Project description:Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation with aberrant epigenetic alterations, leading joint destruction. However, epigenetic regulatory mechanisms underlying RA pathogenesis remain largely unknown. Here we showed that Ubiquitin-like containing PHD and RING finger domains 1 (known as UHRF1) is a central epigenetic regulator to suppressively orchestrate the expression of multiple exacerbation factors in RA. We found remarkable up-regulation of Uhrf1, which is known as a key molecular for maintenance of DNA methylation during cell division 1-3, in murine arthritis tissue, especially synovial fibroblasts (SF). SF-specific Uhrf1 conditional knockout mice indicated more severe arthritic phenotypes with apoptosis resistant SF. Integrative analysis between transcriptome and methylome showed that expression of several cytokines including Ccl20 were up-regulated in Uhrf1-deficient SF. In RA patients, disease activity scores, CCL20 expression, Th17 accumulation, apoptosis resistance were negatively correlated with UHRF1 expression in synovium. Finally, stabilization of UHRF1 by administration of Ryuvidine improved pathogenesis of arthritis model mice. Our results demonstrated that UHRF1 expressed in SF contributes to suppressively orchestrate expression of genes of multiple exacerbating factors under RA progression. Targeting UHRF1 could provide a novel therapeutic strategy for RA.
2021-02-16 | GSE166747 | GEO
Project description:Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation with aberrant epigenetic alterations, leading joint destruction. However, epigenetic regulatory mechanisms underlying RA pathogenesis remain largely unknown. Here we showed that Ubiquitin-like containing PHD and RING finger domains 1 (known as UHRF1) is a central epigenetic regulator to suppressively orchestrate the expression of multiple exacerbation factors in RA. We found remarkable up-regulation of Uhrf1, which is known as a key molecular for maintenance of DNA methylation during cell division 1-3, in murine arthritis tissue, especially synovial fibroblasts (SF). SF-specific Uhrf1 conditional knockout mice indicated more severe arthritic phenotypes with apoptosis resistant SF. Integrative analysis between transcriptome and methylome showed that expression of several cytokines including Ccl20 were up-regulated in Uhrf1-deficient SF. In RA patients, disease activity scores, CCL20 expression, Th17 accumulation, apoptosis resistance were negatively correlated with UHRF1 expression in synovium. Finally, stabilization of UHRF1 by administration of Ryuvidine improved pathogenesis of arthritis model mice. Our results demonstrated that UHRF1 expressed in SF contributes to suppressively orchestrate expression of genes of multiple exacerbating factors under RA progression. Targeting UHRF1 could provide a novel therapeutic strategy for RA.
2021-02-16 | GSE166746 | GEO
Project description:Epigenetic regulator UHRF1 suppressively organize multiple pathogenesis in rheumatoid arthritis.
| PRJNA701897 | ENA
Project description:Epigenetic regulator UHRF1 suppressively organize multiple pathogenesis in rheumatoid arthritis [MBD-seq]
| PRJNA701904 | ENA
Project description:Epigenetic regulator UHRF1 suppressively organize multiple pathogenesis in rheumatoid arthritis [RNA-seq]
| PRJNA701902 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-04-07 | E-GEOD-56544 | biostudies-arrayexpress
Project description:Rheumatoid arthritis (RA) is a systemic autoimmune disease that affects about 1% of the world's population. The etiology of RA remains unknown. It is considered to occur in the presence of genetic and environmental factors. An increasing body of evidence pinpoints that epigenetic modifications play an important role in the regulation of RA pathogenesis. Epigenetics causes heritable phenotype changes that are not determined by changes in the DNA sequence. The major epigenetic mechanisms include DNA methylation, histone proteins modifications and changes in gene expression caused by microRNAs and other non-coding RNAs. These modifications are reversible and could be modulated by diet, drugs, and other environmental factors. Specific changes in DNA methylation, histone modifications and abnormal expression of non-coding RNAs associated with RA have already been identified. This review focuses on the role of these multiple epigenetic factors in the pathogenesis and progression of the disease, not only in synovial fibroblasts, immune cells, but also in the peripheral blood of patients with RA, which clearly shows their high diagnostic potential and promising targets for therapy in the future.
| S-EPMC6587113 | biostudies-literature
Project description:MicroRNAs (miRNAs) play crucial roles in regulating the transcriptome and development of rheumatoid arthritis (RA). Currently, a comprehensive map illustrating how miRNAs regulate transcripts, pathways, immune system differentiation, and their interactions with terminal cells such as fibroblast-like synoviocytes (FLS), immune-cells, osteoblasts, and osteoclasts are still laking. In this review, we summarize the roles of miRNAs in the susceptibility, pathogenesis, diagnosis, therapeutic intervention, and prognosis of RA. Numerous miRNAs are abnormally expressed in cells involved in RA and regulate target genes and pathways, including NF-κB, Fas-FasL, JAK-STAT, and mTOR pathways. We outline how functional genetic variants of miR-499 and miR-146a partly explain susceptibility to RA. By regulating gene expression, miRNAs affect T cell differentiation into diverse cell types, including Th17 and Treg cells, thus constituting promising gene therapy targets to modulate the immune system in RA. We summarize the diagnostic and prognostic potential of blood-circulating and cell-free miRNAs, highlighting the opportunity to combine these miRNAs with antibodies to cyclic citrullinated peptide (ACCP) to allow accurate diagnosis and prognosis, particularly for seronegative patients. Furthermore, we review the evidence implicating miRNAs as promising biomarkers of efficiency and response of, and resistance to, disease-modifying anti-rheumatic drugs and immunotherapy. Finally, we discuss the autotherapeutic effect of miRNA intervention as a step toward the development of miRNA-based anti-RA drugs. Collectively, the current evidence supports miRNAs as interesting targets to better understand the pathogenetic mechanisms of RA and design more efficient therapeutic interventions.
| S-EPMC8987113 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-04-30 | GSE112658 | GEO
Project description:Autoimmune rheumatic diseases, such as Sjögren syndrome (SS) and rheumatoid arthritis (RA), are characterized by chronic inflammation and autoimmunity, which cause joint tissue damage and destruction by triggering reduced mobility and debilitation in patients with these diseases. Initiation and maintenance of chronic inflammatory stages account for several mechanisms that involve immune cells as key players and the interaction of the immune cells with other tissues. Indeed, the overlapping of certain clinical and serologic manifestations between SS and RA may indicate that numerous immunologic-related mechanisms are involved in the physiopathology of both these diseases. It is widely accepted that epigenetic pathways play an essential role in the development and function of the immune system. Although many published studies have attempted to elucidate the relation between epigenetic modifications (e.g. DNA methylation, histone post-translational modifications, miRNAs) and autoimmune disorders, the contribution of epigenetic regulation to the pathogenesis of SS and RA is at present poorly understood. This review attempts to shed light from a critical point of view on the identification of the most relevant epigenetic mechanisms related to RA and SS by explaining intricate regulatory processes and phenotypic features of both autoimmune diseases. Moreover, we point out some epigenetic markers which can be used to monitor the inflammation status and the dysregulated immunity in SS and RA. Finally, we discuss the inconvenience of using epigenetic data obtained from bulk immune cell populations instead specific immune cell subpopulations.
| S-EPMC6863924 | biostudies-literature