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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Skin gene expression correlates of severity of interstitial lung disease in systemic sclerosis

ABSTRACT: We identified eighty two skin transcripts significantly correlated with the severity of interstitial lung disease (ILD) in systemic sclerosis. These genes separated patients with more sever ILD in unsupervised hierarchical clustering. Pathway analysis revealed pathways involved in extravasation and adhesion of inflammatory cells to endothelium. Skin biopsy samples from 59 patients enrolled in the GENISOS cohort or an open label imatinib study were examined by global gene expression studies.

ORGANISM(S): Homo sapiens

SUBMITTER: Jeffrey Chang

PROVIDER: E-GEOD-47162 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Skin gene expression correlates of severity of interstitial lung disease in systemic sclerosis

Project description:We identified eighty two skin transcripts significantly correlated with the severity of interstitial lung disease (ILD) in systemic sclerosis. These genes separated patients with more sever ILD in unsupervised hierarchical clustering. Pathway analysis revealed pathways involved in extravasation and adhesion of inflammatory cells to endothelium.

2013-07-12 | GSE47162 | GEO

Systems biology of interstitial lung diseases

Project description:This SuperSeries is composed of the following subset Series: GSE21369: Gene expression profiles of interstitial lung disease (ILD) patients GSE21394: MicroRNA expression profiles of interstitial lung disease (ILD) patients Refer to individual Series

2011-04-19 | E-GEOD-21411 | biostudies-arrayexpress

Dissecting the heterogeneity of skin gene expression patterns in systemic sclerosis.

Project description:We identified fibro-inflammatory and keratin gene expression signatures in systemic sclerosis skin. Skin biopsy samples from 61 patients enrolled in the GENISOS cohort or an open label imatinib study (baseline sample) and 36 controls were examined by global gene expression studies. 5 patients were sampled at two time points (early-late). There is overlap between this data set and GSE47162.

2015-05-26 | E-GEOD-58095 | biostudies-arrayexpress

Single-cell analysis reveals fibroblast heterogeneity and myofibroblasts in systemic sclerosis-associated interstitial lung disease

Project description:Myofibroblasts are key effector cells in the extracellular matrix remodeling of systemic sclerosis-associated interstitial lung disease (SSc-ILD), however the diversity of fibroblast populations present in the healthy and SSc-ILD lung is unknown, and has prevented the specific study of the myofibroblast transcriptome. We sought to identify and define the transcriptomes of myofibroblasts and other mesenchymal cell populations in human healthy and SSc-ILD lungs to understand how alterations in fibroblast phenotypes lead to SSc-ILD fibrosis.

2019-08-14 | GSE128169 | GEO

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

Project description:Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is the leading cause of death in patients with systemic sclerosis (SSc) with unclear pathogenesis and limited treatment options. Evidence strongly supports an important role for profibrotic, SPP1-expressing macrophages in SSc-ILD. We sought to define the transcriptome and chromatin structural changes of SPP1 SSc-ILD macrophages, so as to better understand their role in promoting fibrosis and to identify transcription factors associated with open chromatin driving their altered phenotype.

2022-09-02 | GSE212109 | GEO

Expression of miRNA from lung tissue from Systemic Sclerosis patients with interstitial lung disease (SSc-ILD) and healthy controls.

Project description:Objective: MicroRNAs (miRNAs) control key elements of mRNA stability and likely contribute to the dysregulated lung gene expression observed in systemic sclerosis associated interstitial lung disease (SSc-ILD). We analyzed the miRNA gene expression of tissue and cells from SSc-ILD patients. A chronic lung fibrotic murine model was used. Methods: RNA was isolated from lung tissue of 12 SSc-ILD patients and 5 control lungs. High-resolution computed tomography (HRCT) was performed at baseline and 2-3 years after treatment. Lung fibroblasts and PBMCs were isolated from healthy controls and SSc-ILD patients. miRNA and mRNA were analyzed by microarray, quantitative polymerase chain reaction, and/or Nanostring; pathway analysis was performed by DIANA-miRPath v2.0 software. Wild-type and miR-155 deficient (miR-155ko) mice were exposed to bleomycin. Results: Lung miRNA microarray data distinguished patients with SSc-ILD from healthy controls with 185 miRNA differentially expressed (q<0.25). DIANA-miRPath revealed 57 KEGGs pathways related to the most dysregulated miRNAs. miR-155 and miR-143 were strongly correlated with progression of the HRCT score. Lung fibroblasts showed only mild expression of miR-155/miR-21 after several stimuli. miR-155 PBMC expression strongly correlated with lung function tests in SSc-ILD. miR-155ko mice developed milder lung fibrosis, survived longer, and showed a weaker lung induction of several genes after bleomycin exposure compared to wild-type mice. Conclusions: miRNAs are dysregulated in lungs and PBMCs of SSc-ILD patients. Based on mRNA-miRNA interaction analysis and pathway tools, miRNAs may play a role in the progression of the disease. Our findings suggest that targeting miR-155 might provide a novel therapeutic strategy for SSc-ILD. Lung biopsies taken from open lung biopsy from SSc-ILD patients (n=15 samples) and from cancer free control patients (n=5) during ressection of the lung tumor.

2016-08-01 | E-GEOD-81293 | biostudies-arrayexpress

CXCR2 may serve as a useful index of disease activity in interstitial lung disease associated with primary Sjögren’s syndrome

Project description:Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease characterized by typical autoantibody production and lymphocytic-mediated exocrine gland damage. Interstitial lung disease (ILD) is a common complication of pSS and can be associated with a poor prognosis. However, the pathogenesis of ILD in pSS is still unclear. In this study, we used RNA sequencing to investigate the gene-expression profile of the minor salivary glands (MSGs) from 36 patients with ILD-pSS and 128 patients with non-ILD-pSS. In the remarkably enriched chemokine-mediated signaling pathway, CXCR2 was found to be significantly elevated in both MSG and plasma from pSS patients with versus without ILD (p < 0.001). Furthermore, the CXCR2 expression level in MSG and plasma was significantly associated with the diffusing capacity of the lungs for carbon monoxide, erythrocyte sedimentation rate, and EULAR Sjögren’s Syndrome Disease Activity Index in ILD-pSS. Therefore, with its potential role in ILD progression in patients with pSS and its strong association with clinical manifestations of the disease, CXCR2 may serve as a useful index for disease activity in ILD associated with pSS.

2021-06-02 | GSE171896 | GEO

Expression of mRNA from lung tissue from Systemic Sclerosis patients with interstitial lung disease (SSc-ILD) and healthy controls (HC)

2016-08-01 | E-GEOD-81292 | biostudies-arrayexpress

Disparate interferon signaling and shared aberrant basaloid cells in single-cell profiling of idiopathic pulmonary fibrosis and systemic sclerosis-associated interstitial lung disease

Project description:Idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) differ in the predominant demographics and identified genetic risk alleles of affected patients, however both diseases frequently progress to respiratory failure and death. Contrasting advanced SSc-ILD to IPF provides insight to the role dysregulated immunity may play in pulmonary fibrosis. To analyze cell-type specific transcriptome commonalities and differences between IPF and SSc-ILD, we compared single-cell RNA-sequencing (scRNA-seq) of 21 explanted lung tissue specimens from patients with advanced IPF, SSc-ILD, and organ donor controls. Comparison of IPF and SSc-ILD tissue identified divergent patterns of interferon signaling, with interferon-gamma signaling upregulated in the SPP1hi and FABP4hi macrophages, cytotoxic T cells, and natural kill cells of IPF, while type I interferon signaling and production was upregulated in the corresponding SSc-ILD populations. Plasmacytoid dendritic cells were found in diseased lungs only, and exhibited upregulated cellular stress pathways in SSc-ILD compared to IPF. Alveolar type I cells were dramatically decreased in both IPF and SSc-ILD, with a distinct transcriptome signature separating these cells by disease. KRT5-/KRT17+ aberrant basaloid cells exhibiting markers of cellular senescence and epithelial-mesenchymal transition were identified in SSc-ILD for the first time. In summary, our study utilizes the enriched capabilities of scRNA-seq to identify key divergent cell types and pathways between IPF and SSc-ILD, providing new insights into the shared and distinct mechanisms between idiopathic and autoimmune interstitial lung diseases.

2021-03-30 | GSE156310 | GEO

Identification and functional prediction of long noncoding RNA and mRNA related to connective tissue disease-associated interstitial lung diseases

Project description:LncRNA microarray analysis was used to identify the pattern of lncRNA and mRNA dysregulation between connective tissue disease-associated interstitial lung diseases (CTD-ILD) and connective tissue disease without associated interstitial lung disease (CTD-NILD). Differential genes were identified by bioinformatic analysis. Relative expression levels of five differentially expressed lncRNAs and one mRNA in 120 CTD patients with or without ILD were detected by quantitative reverse-transcription PCR (qRT-PCR). The differential gene expression analysis revealed 46 lncRNAs and 133 mRNAs were upregulated while 194 lncRNAs and 85 mRNAs were downregulated in the CTD-ILD group compared to the CTD-NILD group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses identified several significant biological processes and signaling pathways, including NF-kappa B signaling pathway, IL-17 signaling pathway, Toll-like receptor signaling pathway, B cell receptor signaling pathway. QRT-PCR confirmed that the selected target genes were differentially expressed in different groups. In particular, the ENST00000604692 expression level was significantly higher in the ILD than the NILD group. This research has demonstrated, for the first time, the specific profile of lncRNA in PBMCs of CTD-ILD patients and the potential signal pathways related to the pathogenesis of CTD-ILD, which may provide newfound insights for the diagnosis and treatment of CTD-ILD patients.

2022-01-05 | GSE192985 | GEO

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