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首页> 外文期刊>American Journal of Physiology >Expression of epithelial sodium channel alpha-subunit mRNAs with alternative 5'-untranslated regions in the developing human lung.
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Expression of epithelial sodium channel alpha-subunit mRNAs with alternative 5'-untranslated regions in the developing human lung.

机译：在发育中的人肺中具有替代性5'-非翻译区的上皮钠通道α-亚基mRNA的表达。

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摘要

In preparation for birth, lung epithelia must switch from net fluid secretion, required for lung development, to net absorption, which prepares the lungs for postnatal gas exchange. The apical membrane amiloride-sensitive epithelial Na channel (ENaC) is the rate-limiting step for Na+ and fluid absorption. Expression of alpha-ENaC mRNA has been detected in human lung as early as the embryonic stage of development. However, humans express multiple transcripts for alpha-ENaC, containing differing 5'-untranslated regions (UTR) with unknown effects on protein translation, and different ontogenies for individual transcripts could provide a novel mechanism for developmental regulation of ENaC function. To assess the relative expression of the two most abundant alpha-ENaC transcripts (alpha-ENaC1 and alpha-ENaC2) during lung development, we performed nonradioactive in situ hybridization using probes specific to the alternative 5'-UTRs. Both transcripts were expressed throughout intrauterine lung development (8to 40 wk gestation), and expression was localized to the surface epithelial cells of the conductive and respiratory airways in both ciliated cells and nonciliated Clara cells. alpha-ENaC mRNA expression was also identified in the serous cells of the submucosal glands surrounding the proximal airways. In the mature prenatal lung, subsets of alveolar type II (ATII) cells expressed one or both of the alpha-ENaC transcripts. Our observations demonstrate that a developmentally regulated switch between alpha-ENaC 5'-UTR variants is not the trigger by which the developing human lung becomes a fluid-absorbing organ at birth, that individual ATII cells express neither, one, or both of the alpha-ENaC transcripts, and that the overall expression is linked to epithelial cell differentiation and lung maturation.
机译：在准备分娩时，肺上皮细胞必须从肺发育所需的净液体分泌转变为净吸收，这为肺进行产后气体交换做好了准备。顶膜阿米洛利敏感的上皮Na通道（ENaC）是Na +和液体吸收的限速步骤。早在胚胎发育阶段就已在人肺中检测到α-ENaCmRNA的表达。然而，人类表达α-ENaC的多个转录本，其中包含不同的5'-非翻译区（UTR），对蛋白质翻译的影响未知，并且单个转录本的不同本体可以为ENaC功能的发育调控提供新的机制。为了评估肺发育过程中两个最丰富的α-ENaC转录本（α-ENaC1和α-ENaC2）的相对表达，我们使用了对5'-UTR特异的探针进行了非放射性原位杂交。两种转录本均在整个子宫内肺发育过程中表达（妊娠8至40 wk），并且表达位于纤毛细胞和非纤毛Clara细胞中的传导和呼吸道的表面上皮细胞。还确定了近端气道周围粘膜下腺浆液细胞中的α-ENaCmRNA表达。在成熟的产前肺中，II型肺泡（ATII）细胞的子集表达一个或两个alpha-ENaC转录物。我们的观察结果表明，α-ENaC5'-UTR变体之间的发育调控开关并不是发育中的人肺在出生时成为吸收液体的器官的触发因素，单个ATII细胞既不表达，也不表达两种α -ENaC转录本，并且整体表达与上皮细胞分化和肺成熟有关。

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