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

53 Scopus citations

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

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Keywords

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

ASJC Scopus subject areas

  • Molecular Biology

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