Abstract
Neutral sphingomyelinase 2 (nSMase2) upregulation was recently demonstrated to serve as a molecular link between smoke inhalation and emphysematous changes in lungs. Here we report that nSMase2 deficit impairs lung development in mice. We have shown previously that fragilitas ossium (fro) mice carry a mutation in the Smpd3 gene, rendering nSMase2 catalytically inactive. Analysis of lung phenotype revealed that fro mice have abnormally enlarged alveoli and increased compliance of the respiratory system, similar to morphological and functional manifestations of emphysema. Analysis of sphingolipid content in fro lungs revealed a decreased level of C14:0 ceramide but no significant alterations in the levels of sphingosine or sphingosine-1-phosphate. Altogether, our data suggest that nSMase2 activity and ceramide level are critical for lung development and function. Based on our data, ceramide can no longer be viewed as a lipid solely detrimental to lung function.
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Acknowledgments
This study was supported by Georgia Health Sciences University intramural grants (PSRP00032 to CP and STP00105W004 to CD), an American Heart Association Grant (0930038N to NVB), and National Institutes of Health Grants (R03HL095440 to EVB, and R01HL080675, R01HL083327, and R01HL067307to ADV). The authors thank Drs. Irina Gorshkova for technical assistance and Ms. Jenna Gallops for help with manuscript preparation.
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Poirier, C., Berdyshev, E.V., Dimitropoulou, C. et al. Neutral sphingomyelinase 2 deficiency is associated with lung anomalies similar to emphysema. Mamm Genome 23, 758–763 (2012). https://doi.org/10.1007/s00335-012-9419-x
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DOI: https://doi.org/10.1007/s00335-012-9419-x