Early growth response gene 1-mediated apoptosis is essential for transforming growth factor beta1-induced pulmonary fibrosis. Academic Article uri icon



  • Fibrosis and apoptosis are juxtaposed in pulmonary disorders such as asthma and the interstitial diseases, and transforming growth factor (TGF)-beta(1) has been implicated in the pathogenesis of these responses. However, the in vivo effector functions of TGF-beta(1) in the lung and its roles in the pathogenesis of these responses are not completely understood. In addition, the relationships between apoptosis and other TGF-beta(1)-induced responses have not been defined. To address these issues, we targeted bioactive TGF-beta(1) to the murine lung using a novel externally regulatable, triple transgenic system. TGF-beta(1) produced a transient wave of epithelial apoptosis that was followed by mononuclear-rich inflammation, tissue fibrosis, myofibroblast and myocyte hyperplasia, and septal rupture with honeycombing. Studies of these mice highlighted the reversibility of this fibrotic response. They also demonstrated that a null mutation of early growth response gene (Egr)-1 or caspase inhibition blocked TGF-beta(1)-induced apoptosis. Interestingly, both interventions markedly ameliorated TGF-beta(1)-induced fibrosis and alveolar remodeling. These studies illustrate the complex effects of TGF-beta(1) in vivo and define the critical role of Egr-1 in the TGF-beta(1) phenotype. They also demonstrate that Egr-1-mediated apoptosis is a prerequisite for TGF-beta(1)-induced fibrosis and remodeling.


  • Lee, Chun Geun
  • Cho, Soo Jung
  • Kang, Min Jong
  • Chapoval, Svetlana P
  • Lee, Patty J
  • Noble, Paul W
  • Yehualaeshet, Teshome
  • Lu, Binfeng
  • Flavell, Richard A
  • Milbrandt, Jeffrey
  • Homer, Robert J
  • Elias, Jack A

publication date

  • August 2, 2004



  • Apoptosis
  • DNA-Binding Proteins
  • Immediate-Early Proteins
  • Pulmonary Fibrosis
  • Transcription Factors
  • Transforming Growth Factor beta


PubMed Central ID

  • PMC2211975

Scopus Document Identifier

  • 3543109115

PubMed ID

  • 15289506

Additional Document Info


  • 200


  • 3