TY - JOUR
T1 - Proapoptotic Bid is required for pulmonary fibrosis
AU - Budinger, G. R.Scott
AU - Mutlu, Gökhan M.
AU - Eisenbart, James
AU - Fuller, Alyson C.
AU - Bellmeyer, Amy A.
AU - Baker, Christina M.
AU - Wilson, Mindy
AU - Ridge, Karen
AU - Barrett, Terrence A.
AU - Lee, Vivian Y.
AU - Chandel, Navdeep S.
PY - 2006/3/21
Y1 - 2006/3/21
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Bcl-2
KW - TGF-β
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U2 - 10.1073/pnas.0507604103
DO - 10.1073/pnas.0507604103
M3 - Article
C2 - 16537427
AN - SCOPUS:33645241270
SN - 0027-8424
VL - 103
SP - 4604
EP - 4609
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
ER -