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Egr-1 Induces a Profibrotic Injury/Repair Gene Program Associated with Systemic Sclerosis

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 re...

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Autores principales: Bhattacharyya, Swati, Sargent, Jennifer L., Du, Pan, Lin, Simon, Tourtellotte, Warren G., Takehara, Kazuhiko, Whitfield, Michael L., Varga, John
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172216/
https://www.ncbi.nlm.nih.gov/pubmed/21931594
http://dx.doi.org/10.1371/journal.pone.0023082
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author Bhattacharyya, Swati
Sargent, Jennifer L.
Du, Pan
Lin, Simon
Tourtellotte, Warren G.
Takehara, Kazuhiko
Whitfield, Michael L.
Varga, John
author_facet Bhattacharyya, Swati
Sargent, Jennifer L.
Du, Pan
Lin, Simon
Tourtellotte, Warren G.
Takehara, Kazuhiko
Whitfield, Michael L.
Varga, John
author_sort Bhattacharyya, Swati
collection PubMed
description 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.
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spelling pubmed-31722162011-09-19 Egr-1 Induces a Profibrotic Injury/Repair Gene Program Associated with Systemic Sclerosis Bhattacharyya, Swati Sargent, Jennifer L. Du, Pan Lin, Simon Tourtellotte, Warren G. Takehara, Kazuhiko Whitfield, Michael L. Varga, John PLoS One Research Article 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. Public Library of Science 2011-09-13 /pmc/articles/PMC3172216/ /pubmed/21931594 http://dx.doi.org/10.1371/journal.pone.0023082 Text en Bhattacharyya et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bhattacharyya, Swati
Sargent, Jennifer L.
Du, Pan
Lin, Simon
Tourtellotte, Warren G.
Takehara, Kazuhiko
Whitfield, Michael L.
Varga, John
Egr-1 Induces a Profibrotic Injury/Repair Gene Program Associated with Systemic Sclerosis
title Egr-1 Induces a Profibrotic Injury/Repair Gene Program Associated with Systemic Sclerosis
title_full Egr-1 Induces a Profibrotic Injury/Repair Gene Program Associated with Systemic Sclerosis
title_fullStr Egr-1 Induces a Profibrotic Injury/Repair Gene Program Associated with Systemic Sclerosis
title_full_unstemmed Egr-1 Induces a Profibrotic Injury/Repair Gene Program Associated with Systemic Sclerosis
title_short Egr-1 Induces a Profibrotic Injury/Repair Gene Program Associated with Systemic Sclerosis
title_sort egr-1 induces a profibrotic injury/repair gene program associated with systemic sclerosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172216/
https://www.ncbi.nlm.nih.gov/pubmed/21931594
http://dx.doi.org/10.1371/journal.pone.0023082
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