Grier David G, Thompson Alexander, Lappin Terence R J, Halliday Henry L
Regional Neonatal Unit, Royal Maternity Hospital, Grosvenor Road, Belfast BT12 6BB, UK.
Neonatology. 2009;96(1):50-60. doi: 10.1159/000201739. Epub 2009 Feb 10.
Genetic processes underlying fetal lung development and maturation are incompletely understood. Better knowledge of these processes would provide insights into the causes of lung malformations and prevention of respiratory distress syndrome and the potential adverse effects of glucocorticoids. Hox genes are involved in the lung branching morphogenesis and maturation of respiratory epithelium, but their expression pattern remains to be defined.
We hypothesized that genes involved in lung branching would be downregulated during early development, whereas those involved in maturation would be unchanged or upregulated.
TaqMan real-time primers and probes were designed for all 39 murine Hox genes, and the murine SP-B gene and transcription profiles of these genes were obtained from whole lungs isolated at e14.5, e16.5, e18.5, e19.5 and postnatal days 1 and 20.
Hox genes in clusters A and B, specifically those between paralog groups 3 and 7, were the most represented, with Hoxa4 and Hoxa5 being the most highly transcribed. A wave of reduced transcription in 16 Hox genes, coincident with increased SP-B transcription, was observed with advancing gestation. Consistently high transcription of Hoxa5 from e14.5 to postnatal day 20 may indicate that sustained transcription is required for normal lung maturation. When e15.5 lungs were cultured with dexamethasone, Hoxb6, Hoxb7 and Hoxb8 levels were significantly upregulated, creating the potential for modulation of diverse downstream target genes.
Improved understanding of the genetic processes underlying lung development afforded by our Q-PCR platform may allow development of more specific methods for inducing fetal lung maturation.
胎儿肺发育和成熟的遗传过程尚未完全明了。深入了解这些过程将有助于洞察肺畸形的成因、预防呼吸窘迫综合征以及了解糖皮质激素的潜在不良影响。Hox基因参与肺的分支形态发生和呼吸上皮的成熟，但其表达模式仍有待确定。
我们假设参与肺分支的基因在早期发育过程中会下调，而参与成熟的基因则保持不变或上调。
针对所有39个小鼠Hox基因设计了TaqMan实时引物和探针，并从妊娠第14.5天、16.5天、18.5天、19.5天以及出生后第1天和第20天分离的全肺中获取这些基因以及小鼠SP - B基因的转录谱。
A簇和B簇中的Hox基因，特别是旁系同源群3和7之间的那些基因，表达最为丰富，其中Hoxa4和Hoxa5转录水平最高。随着妊娠进展，观察到16个Hox基因转录减少，同时SP - B转录增加。从妊娠第14.5天到出生后第20天，Hoxa5持续高转录可能表明正常肺成熟需要持续转录。当妊娠第15.5天的肺用 dexamethasone培养时，Hoxb6、Hoxb7和Hoxb8水平显著上调，这为调节多种下游靶基因创造了可能性。
我们的定量聚合酶链反应平台对肺发育遗传过程的深入了解，可能有助于开发更具特异性的诱导胎儿肺成熟的方法。
