| Summary: | <p>Abstract</p> <p>Background</p> <p>Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels comprised of five similar subunits that influence signal transduction and cell turnover. α<sub>5 </sub>is a structural subunit detected in many non-neuronal tissues; however, its function during pulmonary development is unknown.</p> <p>Results</p> <p>α<sub>5 </sub>was assessed by immunohistochemistry and RT-PCR in mouse lungs from embryonic day (E)13.5 to post-natal day (PN)20. From E13.5 to E18.5, α<sub>5 </sub>expression was primarily observed in primitive airway epithelial cells while mesenchymal expression was faint and sporadic. α<sub>5 </sub>expression was detected throughout the proximal lung at PN1 and extensively expressed in the peripheral lung at PN4, an early stage of murine alveologenesis. An interesting shift occurred wherein α<sub>5 </sub>expression was almost undetectable in the proximal lung from PN4-PN10, but significant localization was again observed at PN20. Transcriptional control of α<sub>5 </sub>was determined by assessing the activity of reporters containing 2.0-kb and 850-bp of the mouse α<sub>5 </sub>promoter. Because perinatal expression of α<sub>5 </sub>was abundant in bronchiolar and alveolar epithelium, we assessed transcriptional control of α<sub>5 </sub>in Beas2B cells, a human bronchiolar epithelial cell line, and A-549 cells, an alveolar type II cell-like human epithelial cell line. Thyroid Transcription Factor-1 (TTF-1), a key transcription regulator of pulmonary morphogenesis, significantly increased α<sub>5 </sub>transcription by acting on both the 2.0-kb and 850-bp α<sub>5 </sub>promoters. Site-directed mutagenesis revealed that TTF-1 activated α<sub>5 </sub>transcription by binding specific TTF-1 response elements. Exogenous TTF-1 also significantly induced α<sub>5 </sub>transcription.</p> <p>Conclusions</p> <p>These data demonstrate that α<sub>5 </sub>is specifically controlled in a temporal and spatial manner during pulmonary morphogenesis. Ongoing research may demonstrate that precise regulation of α<sub>5 </sub>is important during normal organogenesis and misexpression correlates with tobacco related lung disease.</p>
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