Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Epigenetic changes cause aberrantly high expression of SOX11 leading to systemic sclerosis

ABSTRACT: Systemic sclerosis (SSc) is a chronic, heterogenous multisystem connective tissue disease characterized by vascular injury, autoimmunity, and organ fibrosis. Epigenetic modification is thought to be important in the onset and progression of SSc. SOX (SRY-related HMG box) 11 is a transcription factor playing several important roles in organ development in embryos. We have previously shown that dermal fibroblasts derived from SSc patients showed constitutive, high expression of SOX11 and a positive loop formed by SOX11 and periostin in fibroblasts upregulates the TGF- signals, leading to skin fibrosis. However, the mechanism of the aberrant high expression of SOX11 remain unknown in the pathogenesis of SSc. In this study, we found that SOX11 high expression is associated with presence of activating histone marks (H3K27Ac) in SSc dermal fibroblasts. In contrast, normal fibroblasts express low level of SOX11 associated with silencing histone marks H3K27me3. Moreover, using the miRNA microarray method, we identified some miRNAs downregulated in SSc dermal fibroblasts and target SOX11 and overexpression of these miRNAs significantly repressed the expression of SOX11 in SSc dermal fibroblasts. Our findings, taken together, show that epigenetic activation of SOX11 in systemic sclerosis fibroblasts upregulates the SOX11 expression, leading to skin fibrosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE268765 | GEO | 2025/01/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

SOX11 promotes skin fibrosis by inducing fibrotic factors

Project description:In this study, we demonstrated that baseline SOX11 expression was significantly higher in dermal fibroblasts (DFs) isolated from patients with SSc than that in controls, and increased in response to TGF-b. We then showed that SOX11 is involved in the expression of periostin and some periostin-dependent fibrotic factors identified in lung fibroblasts previously. Moreover, we identified some fibrotic factors induced by SOX11 in DNA microarrays combining TGF-b induction and SOX11 knockdown. Finally, we showed that genetic deletion of SOX11 in Postn positive fibroblast cells protects from bleomycin (BLM)-induced skin fibrosis. Altogether, our data indicate that SOX11 and periostin forms a vicious circle and that TGF-b activates this circle specifically in SSc dermal fibroblasts.

2023-01-29 | GSE206473 | GEO

EphB2 Receptor Promotes Dermal Fibrosis in Systemic Sclerosis

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

The Triptryium wilfordii derivative celastrol has anti-fibrotic effects in systemic sclerosis [Spatial Transcriptomics]

Project description:Objectives: Scleroderma (systemic sclerosis, SSc), as a prototypic inflammation-driven fibrotic disease, possesses connective tissue lesions populated with persistently activated myofibroblasts maintained by an mechanotranductive/pro-adhesive signaling loop. Drugs targeting this pathway are therefore of likely therapeutic benefit. The mechanosensitive transcriptional co-activator, yes activated protein-1 (YAP1), is activated in SSc fibroblasts. The terpenoid celastrol has recently been identified as a YAP1 inhibitor: however, if celastrol can alleviate SSc fibrosis is unknown. Methods: Human dermal fibroblasts from healthy individuals and patients with diffuse cutaneous SSc were treated with or without transforming growth factor b1 (TGFb1) in the presence or absence of celastrol. C57BL6J mice were subjected to the inflammatory-driven bleomycin-induced model of skin SSc, in the presence or absence of celastrol. RNA expression was assessed using RNAseq, real-time polymerase chain reaction and spatial transcriptomic analyses. Protein expression was determined using Western blot and enzyme-linked immunosorbent assay. Fibrosis was monitored by hematoxylin and eosin and trichrome staining, and indirect immunofluorescence analysis. Results: In dermal fibroblasts, celastrol impaired the ability of TGFβ1 to induce an SSc-like pattern of gene expression, including the induction of cellular communication network factor 2 (CCN2), collagen I and TGFβ1 protein. Celastrol alleviated the persistent fibrotic phenotype of dermal fibroblasts cultured from lesions of SSc patients. In the bleomycin-induced model of SSc dermatopathology, celastrol inhibited fibrosis and blocked nuclear localization of YAP in myofibroblasts. Conclusion: Our data are consistent with the hypothesis that compounds, such as celastrol, that antagonize the YAP pathway may be potential treatments for SSc skin fibrosis.

2023-11-01 | GSE226760 | GEO

The Triptryium wilfordii derivative celastrol has anti-fibrotic effects in systemic sclerosis [In vivo bulk RNA-seq]

2023-11-01 | GSE226375 | GEO

The Triptryium wilfordii derivative celastrol has anti-fibrotic effects in systemic sclerosis [in vitro bulk RNA-seq]

2023-11-01 | GSE226374 | GEO

Culture and stimulation conditions influence protein expression of primary fibroblasts

Project description:Tissue fibrosis is a common pathway to organ injury and failure. It is characterized by an excessive deposition of extracellular matrix (ECM) in organs. Deciphering the fibrogenic processes is of utmost importance, as there are few effective therapies in fibrotic diseases 1. Systemic sclerosis (SSc) is a prototypical disease where fibroblasts (Fb) are key effector cells as they differentiate into myofibroblasts in response to chronic inflammation under the influence of transforming growth factor beta 1 (TGF-β1) pathway 2–4. In this study, we compared the proteome of primary Fb in different culture and stimulation conditions. Primary dermal normal human Fb were cultured at passage P3, P5 and P7 with and without Fetal Bovine Serum (FBS). At fifth passage, Fb were stimulated or not with different concentrations of recombinant human active TGF-β1 (0.04, 1 and 5 ng/mL) during 24, 48 and 72 hours.

2021-11-03 | PXD025374 | Pride

Collagen 22α1 is a TGFβ early response gene in human skin that mediates the fibroblast to myofibroblast transition

Project description:Systemic sclerosis (SSc) is a complex multi-system autoimmune disease characterized by immune dysregulation, vasculopathy, and organ fibrosis. Skin fibrosis causes high morbidity and impaired quality of life in affected individuals. In this study, we identified the COL22α1 gene associated with the pathogenesis of skin fibrosis through high-throughput RNA sequencing of human skin in organ culture. The expression levels of COL22α1 were significantly increased by TGFβ in ex vivo human skin tissues and normal human skin fibroblasts, while other fibrosis growth factors such as IL-6 and bleomycin modestly increased COL22α1 expression.

2019-04-02 | GSE109350 | GEO

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.

2022-06-29 | PXD025885 | Pride

Expression data from untreated and rottlerin-treated normal and systemic sclerosis-derived human fibroblasts

Project description:PKC-δ inhibition with the selective inhibitor, rottlerin, resulted in potent downregulation of type I collagen expression and production in normal human dermal fibroblasts and abrogated the exaggerated type I collagen production and expression in fibroblasts cultured from affected skin from patients with the fibrosing disorder, systemic sclerosis (SSc). To elucidate the mechanisms involved in the ability of PKC-δ to regulate collagen production in fibroblasts, we examined the effects of PKC-δ inhibition on the transcriptome of normal and SSc-derived human dermal fibroblasts. We used microarrays to detail the effects of PKC-δ inhibition with rottlerin on the transcriptome of normal and SSc-derived human dermal fibroblasts and to identify gene networks that might be involved in the regulation of extracellular matrix by PKC-δ.

2010-08-22 | GSE23741 | GEO

Fn14 antagonist L524-0366 exerts protective effect on fibroblasts

Project description:The expression of TWEAK and Fn14 was increased in early skin lesions of SSc patients. Fn14 expression on human dermal fibroblasts is significantly increased after stimulation with serum from patients with systemic sclerosis. The interplay between TWEAK and Fn14 is pivotal in the fibrotic progression of various autoimmune diseases. These observations implicate the TWEAK/Fn14 signaling pathway may as a critical player in the pathological advancement of systemic sclerosis; however, the precise underlying mechanisms require further clarification. Thus, human dermal fibroblasts were stimulated by serum from systemic sclerosis patients, and with or without the addition of Fn14 antagonists. We then assessed the antifibrotic effects of this antagonist through RNA sequencing, and preliminary exploration of possible molecular mechanisms.

2024-08-05 | GSE273556 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data