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Early growth response gene 1-mediated apoptosis is essential for transforming growth factor beta1-induced pulmonary

Chun Geun Lee1, Soo Jung Cho, Min Jong Kang

  • 1Section of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar St., 441c TAC, New Haven, CT 06520, USA.

The Journal of Experimental Medicine
|August 4, 2004
PubMed

Insights

Transforming growth factor-beta(1) (TGF-β1) induces lung epithelial apoptosis, fibrosis, and remodeling. Blocking apoptosis via Egr-1 or caspase inhibition ameliorates these TGF-β1 effects, revealing apoptosis as a key step.

Area of Science:

  • Pulmonary Medicine
  • Cell Biology
  • Molecular Biology

Background:

  • Fibrosis and apoptosis are key features of lung diseases like asthma.
  • Transforming growth factor-beta(1) (TGF-β1) is implicated in these pulmonary responses.
  • The in vivo roles of TGF-β1 in lung pathogenesis and its relationship with apoptosis remain unclear.

Purpose of the Study:

  • To investigate the in vivo functions of TGF-β1 in the murine lung.
  • To define the relationship between TGF-β1-induced apoptosis and subsequent fibrotic responses.
  • To elucidate the role of early growth response gene (Egr)-1 in TGF-β1-mediated lung remodeling.

Main Methods:

  • Utilized a novel triple transgenic system to target bioactive TGF-β1 to the murine lung.
  • Administered TGF-β1 and observed epithelial apoptosis, inflammation, fibrosis, and tissue remodeling.
  • Investigated the effects of Egr-1 deficiency and caspase inhibition on TGF-β1-induced responses.

Main Results:

  • TGF-β1 induced transient epithelial apoptosis, followed by inflammation, fibrosis, hyperplasia, and honeycombing.
  • Egr-1 deficiency or caspase inhibition blocked TGF-β1-induced apoptosis.
  • Both interventions significantly reduced TGF-β1-induced fibrosis and alveolar remodeling.

Conclusions:

  • TGF-β1 exerts complex in vivo effects on the lung.
  • Egr-1 plays a critical role in the TGF-β1-induced lung phenotype.
  • Egr-1-mediated apoptosis is a prerequisite for TGF-β1-induced pulmonary fibrosis and remodeling.

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