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Identification of lncRNA–miRNA–mRNA networks in circulating exosomes as potential biomarkers for systemic sclerosis

ABSTRACT: This study aimed to analyze potential biomarkers for systemic sclerosis (SSc) by constructing lncRNA–miRNA–mRNA networks in circulating exosomes (cirexos).

ORGANISM(S): Homo sapiens

PROVIDER: GSE224884 | GEO | 2023/02/13

REPOSITORIES: GEO

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Gene expression from human keratinocytes isolated from limited systemic sclerosis (lcSSc) and diffuse systemic sclerosis (dcSSc) skin biopsy

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.

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Epigenetic regulation of profibrotic macrophages in systemic sclerosis- associated interstitial lung disease

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Transcription profiling of human microvascular endothelial cells in systemic sclerosis

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Project description:There are no effective treatments or clinical response markers for systemic sclerosis (SSc). We sought to assess the potential of novel imaging biomarkers and gene expression profiling approaches in a clinical trial of the tyrosine kinase inhibitor dasatinib in SSc patients with interstitial lung disease (SSc-ILD).

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Project description:There is a pressing need to identify early biomarkers of lung involvement in systemic sclerosis (SSc) to start as soon as possible antifibrotic therapy. We aimed to identify extracellular vesicle-derived microRNAs (EV-miRNAs) that are differentially expressed between SSc patients with and without interstitial lung disease (ILD) and explore their diagnostic value. Small EVs derived from plasma were isolated from 20 well-characterised SSc patients with ILD (SSc-ILD, n=10), without ILD (SSc-no ILD, n=10) and 10 matched healthy subjects (HS). Small RNA sequencing was used to identify sEV-miRNAs associated to SSc-ILD.

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IgG from systemic sclerosis patients induce a profibrosing and serotype-dependent phenotype in normal dermal fibroblast: a multi-omics study

Project description:Autoantibodies (Aab) are frequent in systemic sclerosis (SSc). While recognized as potent biomarkers, their pathogenic role is much debated. This study explored the effect of purified IgG from SSc patients on the phenotype and function of healthy dermal fibroblast (FB) using an innovative multi-omics approach.

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Increased CD226 Expression on CD8+ T cells in Patients with Systemic Sclerosis

Project description:Systemic sclerosis (SSc) is an autoimmune disease characterized by vascular damage, and fibrosis of the skin and internal organs. Because activated and oligoclonally expanded CD8+ T cells can be detected in peripheral blood and lung of SSc patients, effector memory CD8+ T cells may play a critical role for organ involvement in SSc; however, the pathogenic functions of effector memory CD8+ T cells remain incompletely understood. Here we performed DNA microarray analysis of the sort-purified effector memory CD8+ T cells from SSc patients and healthy controls, and showed that the expression of genes related to immune response and cell adhesion, including CD226 (also known as DNAX accessory molecule-1, DNAM-1), was significantly altered. Moreover, detailed analysis of CD226 revealed that CD226highCD8+ T cells were increased in SSc patients (mean, 50.7%) compared with healthy controls (32.9%) and were appreciably associated with the severity of skin sclerosis and interstitial lung disease. Further, CD226highCD8+ T cells from SSc patients produced abundant IL-13 and were positively correlated with the cytotoxic capacity of CD8+ T cells against HUVECs. Finally, the neutralization of CD226 impaired IL-13 production and cytolysis against HUVECs. These findings indicate that upregulated CD226 expression on CD8+ T cells reflects disease severity and are involved in SSc pathogenesis via the production of profibrotic IL-13 and endothelial cell injury, and that CD226 may be a useful target in the treatment of SSc. We first purified effector memory CD8+ T cells (CD3+CD8+CD45RO+CD62L+ cells) from peripheral blood by cell sorting and subsequently performed cDNA microarray analysis of the sort-purified effector memory CD8+ T cells from 9 SSc patients and 5 healthy controls.

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Gene expression in limited cutaneous systemic sclerosis skin

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.

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Skin biopsy expression from the faSScinate phase 2 study of tocilizumab in systemic sclerosis

Project description:Gene expression profiling via microarray was performed for control donors and systemic sclerosis (SSc) patients.

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