SUMMARY
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Cigarette smoking has been identified as one of the major risk factors and several predisposing genetic factors have been implicated in the pathogenesis of COPD, including a single nucleotide polymorphism (SNP) in the latent transforming growth factor (TGF)-β binding protein 4 (Ltbp4)-encoding gene. Consistent with this finding, mice with a null mutation of the short splice variant of Ltbp4 (Ltbp4S) develop pulmonary emphysema that is reminiscent of COPD. Here, we report that the mutational inactivation of the antioxidant protein sestrin 2 (sesn2) partially rescues the emphysema phenotype of Ltbp4S mice and is associated with activation of the TGF-β and mammalian target of rapamycin (mTOR) signal transduction pathways. The results suggest that sesn2 could be clinically relevant to patients with COPD who might benefit from antagonists of sestrin function.
Footnotes
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↵* These authors contributed equally to this work
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COMPETING INTERESTS
The authors declare no competing financial interests.
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AUTHOR CONTRIBUTIONS
F.W., S.D.-Z., K.K., T.B., N.W., J.K.-O. and H.v.M. conceived and designed the experiments; F.W., S.D.-Z., K.K., T.B., N.P., R.D. and A.S.-K. performed the experiments; F.W., S.D.-Z., K.K., T.B., N.W., J.K.-O. and H.v.M. analyzed the data; F.W., T.B., N.W. and H.v.M. wrote the paper.
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SUPPLEMENTARY MATERIAL
Supplementary material for this article is available at http://dmm.biologists.org/lookup/suppl/doi:10.1242/dmm.004234/-/DC1
- Received July 28, 2009.
- Accepted October 5, 2009.
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