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Egr-1 induces a profibrotic injury/repair gene program associated with systemic sclerosis.

التفاصيل البيبلوغرافية
العنوان: Egr-1 induces a profibrotic injury/repair gene program associated with systemic sclerosis.
المؤلفون: Swati Bhattacharyya, Jennifer L Sargent, Pan Du, Simon Lin, Warren G Tourtellotte, Kazuhiko Takehara, Michael L Whitfield, John Varga
المصدر: PLoS ONE, Vol 6, Iss 9, p e23082 (2011)
بيانات النشر: Public Library of Science (PLoS), 2011.
سنة النشر: 2011
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: Transforming growth factor-ß (TGF-ß) signaling is implicated in the pathogenesis of fibrosis in scleroderma or systemic sclerosis (SSc), but the precise mechanisms are poorly understood. The immediate-early gene Egr-1 is an inducible transcription factor with key roles in mediating fibrotic TGF-ß responses. To elucidate Egr-1 function in SSc-associated fibrosis, we examined change in gene expression induced by Egr-1 in human fibroblasts at the genome-wide level. Using microarray expression analysis, we derived a fibroblast "Egr-1-responsive gene signature" comprising over 600 genes involved in cell proliferation, TGF-ß signaling, wound healing, extracellular matrix synthesis and vascular development. The experimentally derived "Egr-1-responsive gene signature" was then evaluated in an expression microarray dataset comprising skin biopsies from 27 patients with localized and systemic forms of scleroderma and six healthy controls. We found that the "Egr-1 responsive gene signature" was substantially enriched in the "diffuse-proliferation" subset comprising exclusively of patients with diffuse cutaneous SSc (dcSSc) of skin biopsies. A number of Egr-1-regulated genes was also associated with the "inflammatory" intrinsic subset. Only a minority of Egr-1-regulated genes was concordantly regulated by TGF-ß. These results indicate that Egr-1 induces a distinct profibrotic/wound healing gene expression program in fibroblasts that is associated with skin biopsies from SSc patients with diffuse cutaneous disease. These observations suggest that targeting Egr-1 expression or activity might be a novel therapeutic strategy to control fibrosis in specific SSc subsets.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC3172216?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0023082
URL الوصول: https://doaj.org/article/69140d2364294017bf50e98e9ca86f9b
رقم الأكسشن: edsdoj.69140d2364294017bf50e98e9ca86f9b
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0023082