Published ahead of print on February 16, 2006, doi:10.1165/rcmb.2005-0475OC
© 2006 American Thoracic Society DOI: 10.1165/rcmb.2005-0475OC Identification of P311 as a Potential Gene Regulating Alveolar GenerationDepartment of Medicine and Lung Biology Center, University of California, San Francisco, California; and Department of Medicine, Baylor College of Medicine, Houston, Texas Correspondence and requests for reprints should be addressed to Thiennu H. Vu, Lung Biology Center, Box 2911, University of California San Francisco, San Francisco, CA 94143-2911. E-mail: thiennu.vu{at}ucsf.edu Smoking-related destructive lung diseases such as chronic obstructive pulmonary disease (COPD) and emphysema are a major cause of morbidity and mortality worldwide. The immediate cause of emphysema is the obliteration of alveoli that are key functional units of the lungs where gas exchange takes place. Alveolar generation/regeneration under normal and pathologic conditions is a poorly understood process, but may hold the key to treatment of human emphysema. We used suppression subtractive hybridization to identify genes that may control alveolar generation during periods of pre- and postnatal active alveolar development. P311, a putative neuronal protein originally identified for its high expression in late-stage embryonic brain, was highly differentially expressed during periods of active distal lung morphogenesis. Quantitative real-time RT-PCR showed that the expression of P311 is developmentally regulated, with peak levels occurring during saccular and alveolar formation. Intriguingly, P311 gene expression was significantly decreased in lungs of individuals with emphysema compared with control subjects. Consistent with a role for this gene in alveolar formation, inhibition of alveolization by dexamethasone treatment in vivo resulted in decreased expression of P311. Together our data suggest that P311 expression is tightly regulated during the critical periods of alveolar formation, and that under pathologic conditions, its relative absence may contribute to failure of alveolar regeneration and lead to the development of human emphysema.
Key Words: alveolization • COPD • emphysema • lung development • P311 This article has been cited by other articles:
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