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

Matrix Biol. 2011 May;30(4):235-42. doi: 10.1016/j.matbio.2011.03.005. Epub 2011 Apr 13.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Connective Tissue / physiopathology
  • Early Growth Response Protein 1 / genetics
  • Early Growth Response Protein 1 / metabolism
  • Early Growth Response Transcription Factors / genetics
  • Early Growth Response Transcription Factors / metabolism*
  • Fibroblasts / metabolism
  • Fibrosis / drug therapy
  • Fibrosis / metabolism*
  • Homeostasis
  • Humans
  • Proto-Oncogene Proteins c-abl / metabolism
  • Repressor Proteins / metabolism
  • Scleroderma, Systemic / drug therapy
  • Scleroderma, Systemic / metabolism
  • Transcription, Genetic
  • Transforming Growth Factor beta / metabolism
  • p300-CBP Transcription Factors


  • Early Growth Response Protein 1
  • Early Growth Response Transcription Factors
  • NAB2 protein, human
  • Repressor Proteins
  • Transforming Growth Factor beta
  • p300-CBP Transcription Factors
  • Proto-Oncogene Proteins c-abl