| First Author | Reynolds PR | Year | 2010 |
| Journal | Respir Res | Volume | 11 |
| Pages | 175 | PubMed ID | 21143907 |
| Mgi Jnum | J:170419 | Mgi Id | MGI:4946465 |
| Doi | 10.1186/1465-9921-11-175 | Citation | Reynolds PR, et al. (2010) TTF-1 regulates alpha5 nicotinic acetylcholine receptor (nAChR) subunits in proximal and distal lung epithelium. Respir Res 11:175 |
| abstractText | BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels comprised of five similar subunits that influence signal transduction and cell turnover. alpha5 is a structural subunit detected in many non-neuronal tissues; however, its function during pulmonary development is unknown. RESULTS: alpha5 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, alpha5 expression was primarily observed in primitive airway epithelial cells while mesenchymal expression was faint and sporadic. alpha5 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 alpha5 expression was almost undetectable in the proximal lung from PN4-PN10, but significant localization was again observed at PN20. Transcriptional control of alpha5 was determined by assessing the activity of reporters containing 2.0-kb and 850-bp of the mouse alpha5 promoter. Because perinatal expression of alpha5 was abundant in bronchiolar and alveolar epithelium, we assessed transcriptional control of alpha5 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 alpha5 transcription by acting on both the 2.0-kb and 850-bp alpha5 promoters. Site-directed mutagenesis revealed that TTF-1 activated alpha5 transcription by binding specific TTF-1 response elements. Exogenous TTF-1 also significantly induced alpha5 transcription. CONCLUSIONS: These data demonstrate that alpha5 is specifically controlled in a temporal and spatial manner during pulmonary morphogenesis. Ongoing research may demonstrate that precise regulation of alpha5 is important during normal organogenesis and misexpression correlates with tobacco related lung disease. |
