Identification of lncRNA–miRNA–mRNA networks in circulating exosomes as potential biomarkers for systemic sclerosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE224884 | GEO | 2023/02/13
REPOSITORIES: GEO
Similar Datasets
Project description:Identification of lncRNA–miRNA–mRNA networks in circulating exosomes as potential biomarkers for systemic sclerosis
| PRJNA932851 | ENA
Project description:Interstitial lung disease (ILD) is a major cause of morbidity and mortality in patients with systemic sclerosis (SSc). Although a large proportion of SSc patients have only limited interstitial involvement with an indolent course, in a significant minority ILD is progressive, requiring prompt treatment and careful monitoring. One of the main challenges for the clinician treating this highly variable disease is the early identification of patients at risk of progressive ILD, while avoiding potentially toxic treatments in those whose disease is inherently stable. Easily available and repeatable biomarkers that allow estimation of the risk of ILD progression and early response to treatment are highly desirable. In this paper, we review the evidence for circulating biomarkers with potential roles in diagnosis, monitoring of disease activity, or determining prognosis. Peripheral blood biomarkers offer the advantages of being readily obtained, non-invasive, and serially monitored. Several possible candidates have emerged from studies performed so far, including SP-D, KL-6, and CCL18. Presently however, there are few prospective studies evaluating the predictive ability of prospective biomarkers after adjustment for disease severity. Future carefully designed, prospective studies of well characterised patients with ILD, with optimal definition of disease severity and outcome measures are needed.
| S-EPMC3439977 | biostudies-literature
Project description:Systemic scleroderma (SSc) is an autoimmune disease which results in fibrotic production in the lung. Resultant SSC-pulmonary fibrosis is the main cause of mortality among SSc patients. From high throughput RNAi screening, we uncovered the ubiquitin E3 ligase KLHL42 as a potential pro-fibrotic mediator of TGFb-dependent fibrotic signaling in primary SSc lung fibroblasts. In this analysis, we sought to uncover putative substrates for KLHL42 by comparing SSc lung fibroblasts with control or KLHL42 siRNA prior to TGFb-treatment, lysis, and TUBE precipitation. The resultant pull-down was analyzed with LC-MS/MS.
2020-01-14 | MSV000084800 | MassIVE
Project description:Systemic sclerosis (SSc) is a rare but devastating disease of fibrosis impacting the dermis and multiple organ systems. The prevalence ranges from 4 to 489 cases per million individuals with ten year mortality rates reported around 18 percent. Survival is related to the extent of skin involvement, yet the precise mechanisms driving skin fibrosis in SSc remain unknown. In this study, we analyzed the shared and unique transcriptomic profiles of SSc and normal keratinocytes.
2018-03-21 | GSE81072 | GEO
Project description:Systemic sclerosis (SSc) is an autoimmune disease characterized by clinical heterogeneity, multi-organ involvement, and complex genetic risk. Here, we report the first multi-tissue meta-analysis of ten independent SSc gene expression datasets. We identify a common immune-fibrotic expression axis across all tissues that is associated with the most severe disease phenotypes. The coexpression patterns conserved across tissues and phenotypes were used to query functional genomic networks, which allowed us to identify common and tissue-specific disease drivers. We find evidence of pro-fibrotic macrophages (MØs) in SSc end-target organs. Prominent genes in the skin functional genomic network are associated with SSc genetic risk and are modulated by immunosuppressive treatment in clinical improvers. These data suggest the interactions between T lymphocytes and MØs are a critical driver of disease and implicate MØs as central to SSc pathogenesis. In total, this study presents a mechanism for fibrosis in SSc end-target tissues, a set of putative therapeutic targets for modulating SSc, and a framework for multi-tissue functional genomic studies of complex human disease.
2017-01-01 | GSE76806 | GEO
Project description:Skin gene expression signatures, including intrinsic subset, are associated with improvement during Mycophenolate mofetil (MMF) treatment. Longitudinal SSc patient biopsies and controls were integrated into 83 sample dataset totaling 165 arrays for gene expression and analysis
2014-07-25 | E-GEOD-59785 | biostudies-arrayexpress
Project description:Systemic sclerosis (SSc) is a chronic autoimmune disease characterized with fibrosis of skin and multiple vital organs, but the immunological pathogenesis of SSc remains largely unknown. We show here that microRNA-19b (miR-19b) promotes IL-9-producing CD4+ T cells (Th9) that exacerbate SSc. Specifically, TGF-b plus IL-4 induced expression of TNF receptor associated factor 6 (TRAF6) through phosphorylated Smad3 linker region site Serine 213 (p-Smad3L-Ser213) and activated it through K63 ubiquitination by suppressing the leucine-rich-repeat-containing protein 3 (NLRC3). TRAF6 consequently formed complex with and activated TGF-b activated kinase 1 (TAK1). TAK1 promoted nuclear factor kappa B (NFκB) p65 activation, which then specifically upregulated miR-19b. miR-19b activated Il9 gene expression and promoted Th9 differentiation by directly targeting and suppressing atypical E2F family member E2f8 gene, a repressor for Il9 gene transcription. Importantly, Th9 cells played a critical role in the development and pathogenesis of experimental SSc by promoting the fibrosis in mice induced with Bleomycin. miR-19b and IL-9 were increased in CD4+ T cells in experimental SSc in mice and also in patients with SSc. Strikingly, inhibition of miR-19b resulted in fewer Th9 cells and attenuated fibrotic manifestations and ameliorated the disease in SSc mice. Our study identifies miR-19b as a key factor of Th9 cells that are involved in the pathogenesis of SSc. Our findings should have clinical implications for patients with SSc.
2024-08-21 | GSE269954 | GEO
Project description:Skin systemic sclerosis (Scleroderma, SSc) is an autoimmune disease while its epigenetic regulatory mechanism is not known. We surveyed the genome-wide active regulatory elements in fresh human skin cells, using Assay of Transposase Accessible Chromatin with sequencing (ATAC-seq) in longitudinal skin from healthy volunteers and affected and unaffected skin from patients with SSc. We created robust pipelines that enable accurate single molecule counting and allelic discrimination from clinical material in vivo without clonal expansion. We generated high-resolution epigenetic regulomes of 9 cell types in normal and SSc skins, and identified 106044 cell type specific accessible sites. Motif analysis of these peaks predicted known and novel transcription factors regulating each cell type. For each cell type, we discovered thousands of accessible sites are differential in normal versus unaffected and affected skin from patients with SSc. We predicted novel transcription factors regulating SSc in a cell type specific manner, and predicted the relative contributions of each cell type in driving skin SSc. ATAC-seq also revealed novel elements that escape X chromosome inactivation, which coordinately impact genes with immune function.
2020-10-20 | GSE99702 | GEO
Project description:Patients with the diffuse avascular form of Systemic Sclerosis (SSc) and healthy controls (N) were used as sources of microvascular endothelial cells (MVEC). MVEC were obtained from biopsies of involved skin of the hands in 6 SSc patients and from 6 healthy patients undergoing surgery for traumatic events at the hands. The controls were matched by age and sex to the SSc cases. All patients fulfilled the American College of Rheumatology criteria for SSc, as well as the criteria for the diffuse form of the disease.
2005-08-30 | E-MEXP-417 | biostudies-arrayexpress
Project description:Objectives: Eph/Ephrin cell-cell signaling is emerging as a key player in tissue fibrogenesis. The aim of this study was to test the hypothesis that the receptor tyrosine kinase EphB2 mediates dermal fibrosis in systemic sclerosis (SSc). Methods: We assessed normal and SSc human skin biopsies for EphB2 expression. The in vivo role of EphB2 in skin fibrosis was investigated by subjecting EphB2-knockout mice to both bleomycin-induced and tight skin (Tsk1/+) genetic mouse models. EphB2 kinase-dead and overactive point mutant mice were used to evaluate the role of EphB2 forward signaling in bleomycin-induced dermal fibrosis. In vitro studies were performed on dermal fibroblasts from SSc patients and healthy controls, which was followed by in vivo analysis of fibroblast-specific EphB2 deficient mice. Results: Expression of EphB2 is upregulated in SSc skin tissue and explanted SSc dermal fibroblasts compared to healthy controls. EphB2 expression is elevated in two animal models of dermal fibrosis. In mice, EphB2 drives dermal fibrosis in both the bleomycin and the Tsk1/+ models of skin fibrosis. EphB2 forward signaling is a critical mediator of dermal fibrosis. Transforming growth factor-β (TGFβ) cytokines upregulate EphB2 in dermal fibroblasts via non-canonical TGFβ/SMAD signaling and silencing EphB2 in dermal fibroblasts is sufficient to dampen TGFβ-induced fibroblast-to-myofibroblast differentiation. Moreover, mice with fibroblast-specific deletion of EphB2 showed impaired fibroblast-to-myofibroblast differentiation and reduced skin fibrosis upon bleomycin challenge. Conclusion: Our data implicate EphB2 overexpression and kinase-mediated forward signaling in the development of dermal fibrosis in SSc. EphB2 thus represents a potential new therapeutic target for SSc.
2024-04-10 | GSE253089 | GEO