Quantitation and localization of ENaC subunit expression in fetal, newborn, and adult mouse lung.

Quantitation and localization of ENaC subunit expression in fetal, newborn, and adult mouse lung.
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胎儿、新生儿和成年小鼠肺中 ENaC 亚基表达的定量和定位。

DOI:
10.1165/ajrcmb.20.3.3283
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发表时间:
1999
影响因子:
6.4
通讯作者:
P. Barker
P. Barker
中科院分区:
医学1区
文献类型:
--
作者:
C. Talbot;D. G. Bosworth;E. Briley;D. Fenstermacher;R. Boucher;S. Gabriel;P. Barker

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新生肺通过活跃的 Na+ 转运清除胎儿液体。异三聚体(α、β、γ)上皮 Na+ 通道 ENaC 介导此过程。为了了解发育过程中各个 ENaC 亚基在 Na+ 转运中的作用,我们通过 Northern 印迹分析定量了胎儿、新生儿和成年小鼠肺中的小鼠 ENaC (mENaC) 亚基信使 RNA (mRNA) 表达水平,并通过原位杂交研究了区域表达。 alphamENaC 和 gammamENaC mRNA 表达在胎儿妊娠晚期急剧增加,并在出生后第 1 天达到接近成人水平。 betamENaC 表达在胎儿晚期和产后早期逐渐增加,并逐渐增加直至成年。原位杂交研究表明,胎儿和出生后肺部的 alphamENaC 和 gammamENaC 亚基表达具有相似的定位模式。 gammamENaC 和 alphamENaC 亚基最初定位于胎儿肺芽小管,到妊娠晚期,这两个亚基在远端肺上皮的所有区域(腺泡和细支气管)中表达。 betamENaC 从妊娠第 16 天起就被检测到,并且在小气道中表达最强烈。 betamENaC 在肺泡区几乎没有表达。在出生后的肺部,所有三个亚基均在小气道中强烈表达。在成人肺中,alphamENaC 和 gammamENaC 的表达模式与肺泡 II 型 (ATII) 细胞分布一致。 mENaC 亚基表达量变化的时间与 Na+ 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产后小鼠肺液体吸收的主要位置。
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.
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