Early growth response transcription factors: Key mediators of fibrosis and novel targets for anti-fibrotic therapy

Swati Bhattacharyya, Minghua Wu, Feng Fang, Warren Tourtellotte, Carol Feghali-Bostwick, John Varga*

*Corresponding author for this work

Research output: Contribution to journalReview article

51 Citations (Scopus)

Abstract

Fibrosis is a deregulated and ultimately defective form of tissue repair that underlies a large number of chronic human diseases, as well as obesity and aging. The pathogenesis of fibrosis involves multiple cell types and extracellular signals, of which transforming growth factor-ß (TGF-ß) is pre-eminent. The prevalence of fibrosis is rising worldwide, and to date no agents has shown clinical efficacy in the attenuating or reversing the process. Recent studies implicate the immediate-early response transcription factor Egr-1 in the pathogenesis of fibrosis. Egr-1 couples acute changes in the cellular environment to sustained alterations in gene expression, and mediates a broad spectrum of biological responses to injury and stress. In contrast to other ligand-activated transcription factors such as NF-κB, c-jun and Smad2/3 that undergo post-translational modification such as phosphorylation and nuclear translocation, Egr-1 activity is regulated via its biosynthesis. Aberrant Egr-1 expression or activity is implicated in cancer, inflammation, atherosclerosis, and ischemic injury and recent studies now indicate an important role for Egr-1 in TGF-ß-dependent profibrotic responses. Fibrosis in various animal models and human diseases such as scleroderma (SSc) and idiopathic pulmonary fibrosis (IPF) is accompanied by aberrant Egr-1 expression. Moreover Egr-1 appears to be required for physiologic and pathological connective tissue remodeling, and Egr-1-null mice are protected from fibrosis. As a novel profibrotic mediator, Egr-1 thus appears to be a promising potential target for the development of anti-fibrotic therapies.

Original languageEnglish (US)
Pages (from-to)235-242
Number of pages8
JournalMatrix Biology
Volume30
Issue number4
DOIs
StatePublished - May 1 2011

Fingerprint

Early Growth Response Transcription Factors
Fibrosis
Transforming Growth Factors
Transcription Factors
Therapeutics
Animal Disease Models
Idiopathic Pulmonary Fibrosis
Wounds and Injuries
Post Translational Protein Processing
Connective Tissue
Atherosclerosis
Chronic Disease
Obesity
Phosphorylation
Ligands
Inflammation
Gene Expression

Keywords

  • Egr-1
  • Fibroblast
  • Fibrosis
  • Scleroderma (systemic sclerosis)
  • TGF-ß

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Bhattacharyya, Swati ; Wu, Minghua ; Fang, Feng ; Tourtellotte, Warren ; Feghali-Bostwick, Carol ; Varga, John. / Early growth response transcription factors : Key mediators of fibrosis and novel targets for anti-fibrotic therapy. In: Matrix Biology. 2011 ; Vol. 30, No. 4. pp. 235-242.
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Early growth response transcription factors : Key mediators of fibrosis and novel targets for anti-fibrotic therapy. / Bhattacharyya, Swati; Wu, Minghua; Fang, Feng; Tourtellotte, Warren; Feghali-Bostwick, Carol; Varga, John.

In: Matrix Biology, Vol. 30, No. 4, 01.05.2011, p. 235-242.

Research output: Contribution to journalReview article

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T2 - Key mediators of fibrosis and novel targets for anti-fibrotic therapy

AU - Bhattacharyya, Swati

AU - Wu, Minghua

AU - Fang, Feng

AU - Tourtellotte, Warren

AU - Feghali-Bostwick, Carol

AU - Varga, John

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N2 - Fibrosis is a deregulated and ultimately defective form of tissue repair that underlies a large number of chronic human diseases, as well as obesity and aging. The pathogenesis of fibrosis involves multiple cell types and extracellular signals, of which transforming growth factor-ß (TGF-ß) is pre-eminent. The prevalence of fibrosis is rising worldwide, and to date no agents has shown clinical efficacy in the attenuating or reversing the process. Recent studies implicate the immediate-early response transcription factor Egr-1 in the pathogenesis of fibrosis. Egr-1 couples acute changes in the cellular environment to sustained alterations in gene expression, and mediates a broad spectrum of biological responses to injury and stress. In contrast to other ligand-activated transcription factors such as NF-κB, c-jun and Smad2/3 that undergo post-translational modification such as phosphorylation and nuclear translocation, Egr-1 activity is regulated via its biosynthesis. Aberrant Egr-1 expression or activity is implicated in cancer, inflammation, atherosclerosis, and ischemic injury and recent studies now indicate an important role for Egr-1 in TGF-ß-dependent profibrotic responses. Fibrosis in various animal models and human diseases such as scleroderma (SSc) and idiopathic pulmonary fibrosis (IPF) is accompanied by aberrant Egr-1 expression. Moreover Egr-1 appears to be required for physiologic and pathological connective tissue remodeling, and Egr-1-null mice are protected from fibrosis. As a novel profibrotic mediator, Egr-1 thus appears to be a promising potential target for the development of anti-fibrotic therapies.

AB - Fibrosis is a deregulated and ultimately defective form of tissue repair that underlies a large number of chronic human diseases, as well as obesity and aging. The pathogenesis of fibrosis involves multiple cell types and extracellular signals, of which transforming growth factor-ß (TGF-ß) is pre-eminent. The prevalence of fibrosis is rising worldwide, and to date no agents has shown clinical efficacy in the attenuating or reversing the process. Recent studies implicate the immediate-early response transcription factor Egr-1 in the pathogenesis of fibrosis. Egr-1 couples acute changes in the cellular environment to sustained alterations in gene expression, and mediates a broad spectrum of biological responses to injury and stress. In contrast to other ligand-activated transcription factors such as NF-κB, c-jun and Smad2/3 that undergo post-translational modification such as phosphorylation and nuclear translocation, Egr-1 activity is regulated via its biosynthesis. Aberrant Egr-1 expression or activity is implicated in cancer, inflammation, atherosclerosis, and ischemic injury and recent studies now indicate an important role for Egr-1 in TGF-ß-dependent profibrotic responses. Fibrosis in various animal models and human diseases such as scleroderma (SSc) and idiopathic pulmonary fibrosis (IPF) is accompanied by aberrant Egr-1 expression. Moreover Egr-1 appears to be required for physiologic and pathological connective tissue remodeling, and Egr-1-null mice are protected from fibrosis. As a novel profibrotic mediator, Egr-1 thus appears to be a promising potential target for the development of anti-fibrotic therapies.

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