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*

*Corresponding author for this work

Research output: Contribution to journalArticle

78 Scopus citations

Abstract

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 (US)
Pages (from-to)4604-4609
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number12
DOIs
StatePublished - Mar 21 2006

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Keywords

  • Apoptosis
  • Bcl-2
  • TGF-β

ASJC Scopus subject areas

  • General

Cite this

Budinger, G. R. S., Mutlu, G. M., Eisenbart, J., Fuller, A. C., Bellmeyer, A. A., Baker, C. M., Wilson, M., Ridge, K., Barrett, T. A., Lee, V. Y., & Chandel, N. S. (2006). Proapoptotic Bid is required for pulmonary fibrosis. Proceedings of the National Academy of Sciences of the United States of America, 103(12), 4604-4609. https://doi.org/10.1073/pnas.0507604103