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Title: A profibrotic gene expression program induced by Egr-1 in skin fibroblasts      
keywords:
Transcriptome or Gene expression
ID:
PRJNA137379
description:
Systemic sclerosis (SSc) is characterized by vascular damage, autoimmunity and fibrosis and is associated with highly variable clinical presentation and disease course. Aberrant transforming growth factor-ß (TGF-ß) signaling via the early immediate transcription factor Egr-1 is implicated in the pathogenesis of SSc. To shed light on the role of Egr-1 in fibrosis, regulation of gene expression in human skin fibroblasts overexpressing Egr-1 was examined by genome-wide expression analysis. Over 600 genes were found to be regulated by Egr-1. The Egr-1-responsive gene signature is largely comprised of genes involved in cell proliferation, TGF-ß signaling, wound healing, extracellular matrix synthesis and vascular development. Expression of the Egr-1 responsive genes was evaluated in a microarray dataset comprising skin biopsies from 17 patients with scleroderma and six healthy controls (GEO GSE9285; PMID 18648520). The “Egr-1 responsive gene signature” was enriched in the ‘diffuse-proliferation’ subset of skin biopsies in the patients with diffuse cutaneous SSc (dcSSc), but was not associated with other forms of scleroderma, or with healthy controls. Skin biopsies from patients with scleroderma can provide more insights into the relevant pathological processes in the subset of disease and could be developed into a diagnostic tool for identifying a subset of diffuse scleroderma patients who may be responsive to Egr-1 therapy. Overall design: Cultures of primary fibroblasts from neonatal foreskin treated by Egr1 and Tgfb1 were measured at 24 and 48 hours. Control samples without any treatment were also measured at the same time points. Two biological replicates per condition/time point were measured using the Illumina HumanRef-8 V2 Expression BeadChip.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA137379
authentication:
none
authorization:
none
ID:
pmid:21931594
dateReleased:
10-26-2011
name:
Homo sapiens
ncbiID:
ncbitax:9606
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject