Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
Respir Res. 2011 Jun 17;12(1):82. doi: 10.1186/1465-9921-12-82.
α5 nicotinic acetylcholine receptor (nAChR) subunits structurally stabilize functional nAChRs in many non-neuronal tissue types. The expression of α5 nAChR subunits and cell-specific markers were assessed during lung morphogenesis by co-localizing immunohistochemistry from embryonic day (E) 13.5 to post natal day (PN) 20. Transcriptional control of α5 nAChR expression by FoxA2 and GATA-6 was determined by reporter gene assays.
Steady expression of α5 nAChR subunits was observed in distal lung epithelial cells during development while proximal lung expression significantly alternates between abundant prenatal expression, absence at PN4 and PN10, and a return to intense expression at PN20. α5 expression was most abundant on luminal edges of alveolar type (AT) I and ATII cells, non-ciliated Clara cells, and ciliated cells in the proximal lung at various periods of lung formation. Expression of α5 nAChR subunits correlated with cell differentiation and reporter gene assays suggest expression of α5 is regulated in part by FoxA2, with possible cooperation by GATA-6.
Our data reveal a highly regulated temporal-spatial pattern of α5 nAChR subunit expression during important periods of lung morphogenesis. Due to specific regulation by FoxA2 and distinct identification of α5 in alveolar epithelium and Clara cells, future studies may identify possible mechanisms of cell differentiation and lung homeostasis mediated at least in part by α5-containing nAChRs.
α5 型烟碱型乙酰胆碱受体（nAChR）亚基在许多非神经元组织类型中结构上稳定功能性 nAChR。通过对胚胎期 13.5 天（E）至出生后 20 天（PN）的免疫组织化学进行共定位，评估了α5 nAChR 亚基和细胞特异性标志物在肺形态发生过程中的表达。通过报告基因测定确定了 FoxA2 和 GATA-6 对α5 nAChR 表达的转录控制。
在发育过程中，α5 nAChR 亚基在远端肺上皮细胞中持续表达，而近端肺表达则在产前表达丰富、PN4 和 PN10 时不存在以及 PN20 时恢复强烈表达之间明显交替。α5 表达在肺泡型（AT）I 和 ATII 细胞、非纤毛 Clara 细胞和近端肺中的纤毛细胞的腔边缘最为丰富，在肺形成的各个时期。α5 nAChR 亚基的表达与细胞分化相关，报告基因测定表明α5 的表达部分受 FoxA2 调节，可能与 GATA-6 合作。
我们的数据揭示了α5 nAChR 亚基在肺形态发生的重要时期表达的高度调控时空模式。由于 FoxA2 的特异性调节以及α5 在肺泡上皮细胞和 Clara 细胞中的独特鉴定，未来的研究可能会确定至少部分通过包含α5 的 nAChR 介导的细胞分化和肺稳态的可能机制。
