Proapoptotic Bid is required for pulmonary fibrosis

G. R.Scott Budinger, Gökhan M. Mutlu, James Eisenbart, Alyson C. Fuller, Amy A. Bellmeyer, Christina M. Baker, Mindy Wilson, Karen Ridge, Terrence A. Barrett, Vivian Y. Lee, Navdeep S. Chandel

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


The molecular mechanisms of pulmonary fibrosis are poorly understood. Previous reports indicate that activation of TGF-β1 is essential for the development of pulmonary fibrosis. Here, we report that the proapoptotic Bcl-2 family member Bid is required for the development of pulmonary fibrosis after the intratracheal instillation of bleomycin. Mice lacking Bid exhibited significantly less pulmonary fibrosis in response to bleomycin compared with WT mice. The attenuation in pulmonary fibrosis was observed despite similar levels of inflammation, lung injury, and active TGF-β1 in bronchoalveolar lavage fluid 5 days after the administration of bleomycin in mice lacking Bid and in WT controls. Bleomycin induced similar levels cell death in vitro in alveolar epithelial cells isolated from WT and bid-/- mice. By contrast, alveolar epithelial cells from bid-/- mice were resistant to TGF-β1-induced cell death. These results indicate that Bcl-2 family members are critical regulators for the development of pulmonary fibrosis downstream of TGF-β1 activation.

Original languageEnglish
Pages (from-to)4604-4609
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - Mar 21 2006


  • Apoptosis
  • Bcl-2
  • TGF-β

ASJC Scopus subject areas

  • General


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