Talbot C L, Bosworth D G, Briley E L, Fenstermacher D A, Boucher R C, Gabriel S E, Barker P M
School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7220, USA.
Am J Respir Cell Mol Biol. 1999 Mar;20(3):398-406. doi: 10.1165/ajrcmb.20.3.3283.
The newborn lung is cleared of fetal liquid by active Na+ transport. The heterotrimeric (alpha, beta, gamma) epithelial Na+ channel, ENaC, mediates this process. To understand the role of individual ENaC subunits in Na+ transport during development, we quantified murine ENaC (mENaC) subunit messenger RNA (mRNA) expression levels of fetal, neonatal, and adult mouse lung by Northern blot analysis and studied regional expression by in situ hybridization. alphamENaC and gammamENaC mRNA expression increased sharply in late fetal gestation and reached near-adult levels by Day 1 of postnatal life. betamENaC expression increased more gradually through late fetal and early postnatal life and increased progressively until adulthood. In situ hybridization studies showed similar localization patterns of alphamENaC and gammamENaC subunit expression in fetal and postnatal lung. gammamENaC and alphamENaC subunits were initially localized to fetal lung bud tubules and by late gestation both subunits were expressed in all regions (acinar and bronchiolar) of the distal lung epithelium. betamENaC was detected from 16 d gestation onward and was expressed most intensely in small airways. There was little expression of betamENaC in the alveolar region. In postnatal lung all three subunits were expressed intensely in small airways. In adult lung, alphamENaC and gammamENaC were expressed in a pattern consistent with an alveolar type II (ATII) cell distribution. The timing of quantitative changes in mENaC subunit expression is consistent with a role of Na+ transport in liquid clearance of the perinatal lung. Intense expression of mENaC subunits in medium and small airway epithelium and in ATII cells suggests that these regions are a primary location for liquid absorption in the perinatal and postnatal murine lung.
新生儿肺通过主动钠转运清除胎儿期液体。异源三聚体（α、β、γ）上皮钠通道（ENaC）介导这一过程。为了解发育过程中单个ENaC亚基在钠转运中的作用，我们通过Northern印迹分析定量检测了胎鼠、新生鼠和成年鼠肺中鼠ENaC（mENaC）亚基信使核糖核酸（mRNA）的表达水平，并通过原位杂交研究了区域表达情况。αmENaC和γmENaC mRNA表达在胎儿妊娠后期急剧增加，并在出生后第1天达到接近成年的水平。βmENaC表达在胎儿后期和出生后早期逐渐增加，并持续增加直至成年。原位杂交研究显示，αmENaC和γmENaC亚基在胎儿和出生后肺中的表达定位模式相似。γmENaC和αmENaC亚基最初定位于胎儿肺芽小管，到妊娠后期，这两个亚基在远端肺上皮的所有区域（腺泡和细支气管）均有表达。βmENaC从妊娠16天开始检测到，在小气道中表达最为强烈。在肺泡区域几乎没有βmENaC的表达。在出生后肺中，所有三个亚基在小气道中均有强烈表达。在成年肺中，αmENaC和γmENaC的表达模式与II型肺泡上皮细胞（ATII）分布一致。mENaC亚基表达的定量变化时间与钠转运在围产期肺液体清除中的作用一致。mENaC亚基在中小气道上皮和ATII细胞中的强烈表达表明，这些区域是围产期和出生后鼠肺液体吸收的主要部位。
