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Systemic and cell type-specific gene expression patterns in scleroderma skin

ABSTRACT: Abstract: We used DNA microarrays representing >12,000 human genes to characterize gene expression patterns in skin biopsies from individuals with a diagnosis of systemic sclerosis with diffuse scleroderma. We found consistent differences in the patterns of gene expression between skin biopsies from individuals with scleroderma and those from normal, unaffected individuals. The biopsies from affected individuals showed nearly indistinguishable patterns of gene expression in clinically affected and clinically unaffected tissue, even though these were clearly distinguishable from the patterns found in similar tissue from unaffected individuals. Genes characteristically expressed in endothelial cells, B lymphocytes, and fibroblasts showed differential expression between scleroderma and normal biopsies. Analysis of lymphocyte populations in scleroderma skin biopsies by immunohistochemistry suggest the B lymphocyte signature observed on our arrays is from CD20+ B cells. These results provide evidence that scleroderma has systemic manifestations that affect multiple cell types and suggests genes that could be used as potential markers for the disease This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE4385 | GEO | 2006/03/08

SECONDARY ACCESSION(S): PRJNA94567

REPOSITORIES: GEO

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Systemic and cell type-specific gene expression patterns in scleroderma skin

Project description:This SuperSeries is composed of the following subset Series: GSE3886: Scleroderma Morphea Normal Fibroblasts GSE3887: Scleroderma Architecture Cell Lines Abstract: We used DNA microarrays representing >12,000 human genes to characterize gene expression patterns in skin biopsies from individuals with a diagnosis of systemic sclerosis with diffuse scleroderma. We found consistent differences in the patterns of gene expression between skin biopsies from individuals with scleroderma and those from normal, unaffected individuals. The biopsies from affected individuals showed nearly indistinguishable patterns of gene expression in clinically affected and clinically unaffected tissue, even though these were clearly distinguishable from the patterns found in similar tissue from unaffected individuals. Genes characteristically expressed in endothelial cells, B lymphocytes, and fibroblasts showed differential expression between scleroderma and normal biopsies. Analysis of lymphocyte populations in scleroderma skin biopsies by immunohistochemistry suggest the B lymphocyte signature observed on our arrays is from CD20+ B cells. These results provide evidence that scleroderma has systemic manifestations that affect multiple cell types and suggests genes that could be used as potential markers for the disease Refer to individual Series

2006-03-07 | E-GEOD-4385 | biostudies-arrayexpress

Transcription profiling of human skin biopsies from individuals with a diagnosis of systemic sclerosis with diffuse scleroderma vs biopsies from normal individiduals

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Transcription profiling of human skin bioposis from patients with diffuse scleroderma and limited scleroderma

Project description:RNA expression profiling was carried out for systemic sclerosis (scleroderma) on skin biopsies obtained from both diffuse scleroderma (dcSSc) and limited scleroderma (lcSSc) subjects patients and compared to normal subjects. The patient group comprised of 4 dcSSc and 2 lcSSc subjects, all of whom were Caucasian and belonged to the age range of 42-73 (Mean age = 61.6). Patient sample set consisted of 3 females and 3 males. Race matched female volunteers from the same geographical area were recruited as controls (n = 4) and belonged to the age range of 41-62 (Mean age = 52).

2015-03-25 | E-MEXP-1214 | biostudies-arrayexpress

Real-time quantitative PCR analysis of 88 microRNAs involved in human cell differentiation and development in involved skin of systemic scleroderma (SSc), localized scleroderma (LSc) and Keloid.

Project description:Skin specimens were derived from involved skin of 3 systemic scleroderma (SSc), 3 localized scleroderma (LSc) and 3 keloid patients. These skin samples and 3 control skins were collected and fixed in formaldehyde immediately after resections. The microRNA (miRNA) isolation from human skin tissue was performed using miRNeasy FFPE kit (Qiagen). For PCR array, miRNAs were reverse-transcribed into first strand cDNA using RT2 miRNA First Strand Kit (SABiosciences). A mixture of equal amounts of miRNAs from 3 normal skins, 3 SSc, 3 LSc or 3 keloid were prepared, and miRNA expression profile in each disease in vivo was evaluated using RT2 Profiler PCR Array. The cDNA was mixed with RT2 SYBR Green/ROX qPCR Master Mix and the mixture was added into 96-well RT2 miRNA PCR Array that includes primer pairs for 88 human miRNAs (SABiosciences). Skin specimens were derived from involved skin of 3 systemic scleroderma (SSc), 3 localized scleroderma (LSc) and 3 keloid patients. These skin samples and 3 control skins were collected and fixed in formaldehyde immediately after resections. Control donors were each matched with diseases for age, sex, and biopsy site.

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Inhibition of histone readers bromodomain extra-terminal proteins alleviates scleroderma fibrosis

Project description:We assessed transcriptomic changes in fibroblasts isolated from skin biopsies from diffuse cutaneous scleroderma patients before and after BET inhibitor JQ1 treatment

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Gene Expression Profiling of Scleroderma Skin

Project description:We have analyzed the genome-wide patterns of gene expression with DNA microarrays in skin biopsies from 34 subjects: 17 patients with SSc with diffuse scleroderma (dSSc), 7 patients with SSc with limited scleroderma (lSSc), 3 patients with morphea and 6 healthy controls. In total, 61 skin biopsies were analyzed. The addition of 14 technical replicates resulted in a total of 75 microarray hybridizations. The Intrinsic_scleroderma_genes.txt supplementary file lists the 995 genes with the most consistent expression between each forearm-back pair and technical replicates, but with the highest variance across all samples analyzed. An intrinsic gene identifier algorithm was used to select a set of intrinsic scleroderma genes. A total of 34 experimental groups were defined, each representing the 34 different subjects in our study. Replicate hybridizations for a given patient were assigned to the same experimental group. Each gene was analyzed and assigned a score that is inversely related to how intrinsic the gene's expression is across the samples analyzed. The analysis was repeated on randomized data in order to estimate a False Discovery Rate (FDR). An intrinsic score of 0.3 selected 995 genes with an FDR of 4% (39 ± 7 genes) while retaining reproducible clustering of technical replicates. Keywords: global gene expression profiling using Agilent Whole Human genome oligo arrays

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Scleroderma Morphea Normal Fibroblasts

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2005-12-20 | E-GEOD-3886 | biostudies-arrayexpress

Scleroderma Morphea Normal Fibroblasts

2005-12-21 | GSE3886 | GEO

A bleomycin induced murine model of scleroderma in GSDMD-/- versus wild type

Project description:The NLRP3 inflammasome and IL-1β are essential for scleroderma pathogenesis. Nevertheless, the role of pyroptosis executor gasdermin D(GSDMD), which is a downstream molecule of NLRP3 and is required for IL-1β release in some situations, has not yet been well elucidated in scleroderma. The purpose of this study was to explore the differences in the degree of skin fibrosis between GSDMD-/- and wild type mice in a bleomycin-induced scleroderma model, and the molecular pathways that may be involved.Total RNA from skin biopsies from GSDMD-/- and wild type mice after subcutaneous injection of BLM to induce skin fibrosis was examined by nextGen RNA sequencing

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RNA-Seq analysis of skin from bleomycin induced scleroderma murine models treated with EHP-101

Project description:Systemic sclerosis (SSc) or scleroderma is a chronic multiorgan autoimmune disease of unknown etiology characterized by vascular, immunological and fibrotic abnormalities. Several lines of evidence have shown that the endocannabinoid system (ECS) may play a role in the pathophysiology of SSc. VCE-004.8, a CBD aminoquinone derivative, is a dual PPARγ/CB2 that alleviates bleomycin (BLM)-induced skin fibrosis. Herein we report that EHP-101, an oral lipidic formulation of VCE-004.8, prevents skin and lung fibrosis and collagen accumulation in BLM challenged mice. Immunohistochemistry analysis of the skin demonstrate that EHP-101 prevents macrophage infiltration, and the expression of Tenascin C (TNC), VCAM, and the α-smooth muscle actin (SMA). In addition, a reduced expression of vascular CD31, paralleling skin fibrosis, was also prevented by EHP-101. RNAseq analysis in skin biopsies showed a clear effect of EHP-101 in the inflammatory and epithelial-mesenchymal transition transcriptomic signatures. TGF-beta regulated genes such as matrix metalloproteinase-3 (Mmp3), cytochrome b-245 heavy chain (Cybb), lymphocyte antigen 6E (Ly6e), vascular cell adhesion molecule-1 (Vcam1) and the Integrin alpha-5 (Itga5) were induced in BLM mice and repressed by EHP-101 treatment. We also intersected differentially expressed genes in EHP-101-treated mice with dataset of human scleroderma intrinsic genes and found 53 overlapped genes, including the C-C motif chemokine 2 (Ccl2) and the interleukin 13 receptor subunit alpha 1 (IL-13Ra1) genes, which have been studied as biomarkers of SSc. Altogether the results indicate that this synthetic cannabinoid qualifies as a novel compound for the management and possible treatment of scleroderma and, potentially, other fibrotic diseases.

2018-10-02 | GSE115503 | GEO

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