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Endogenous and exogenous glucocorticoid regulation of ENaC mRNA expression in developing kidney and lung.

机译:内源性和外源性糖皮质激素对发育中的肾脏和肺中ENaC mRNA表达的调节。

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Lung liquid absorption at birth is crucial for the successful onset of respiration. Na absorption by the renal collecting duct plays an important role in renal fluid and electrolyte homeostasis during the early postnatal period. The epithelial Na channel (ENaC) plays a central role in mediating these functions, and its subunit expression is developmentally regulated in a temporal and tissue specific pattern. Several lines of evidence suggest that the prenatal increase in circulating glucocorticoids may play an important role in increasing ENaC expression during maturation. We tested the role of the prenatal surge using corticotropin-releasing hormone (CRH) knockout (KO) mice. Relative ENaC expression in lungs of KO mice increased at the same rate as in wild-type (WT) mice, but absolute expression was only 20-30% of WT. In contrast, relative and absolute expression of all three subunits in kidneys was not different between KO and WT mice. Dexamethasone (Dex) increased alpha-ENaC mRNA in fetal lung and kidney explants within 24 h but had different effects on beta- or gamma-ENaC. Dex increased beta- and gamma-ENaC in lung, but only after >48 h of exposure, and had no effect on kidney. The results suggest that the kidney metabolizes endogenous glucocorticoids, but the lung does not. Furthermore, the marked difference between lung and kidney responsiveness to glucocorticoids in beta- and gamma-ENaC expression suggests that factors other than steroids may be important in regulating functional ENaC expression during development.
机译:出生时吸收肺液对于成功开始呼吸至关重要。产后早期,肾收集管对钠的吸收在肾液和电解质稳态中起重要作用。上皮Na通道(ENaC)在介导这些功能中起着核心作用,其亚基表达受时间和组织特异性模式的发育调节。有几条证据表明,产前循环糖皮质激素的增加可能在成熟过程中增加ENaC表达中起重要作用。我们使用促肾上腺皮质激素释放激素(CRH)敲除(KO)小鼠测试了产前激增的作用。 KO小鼠肺中的相对ENaC表达以与野生型(WT)小鼠相同的速率增加,但绝对表达仅为WT的20-30%。相反,KO和WT小鼠在肾脏中所有三个亚基的相对和绝对表达没有差异。地塞米松(Dex)在24小时内增加了胎儿肺和肾脏外植体中的α-ENaCmRNA,但对β-或γ-ENaC的影响不同。 Dex增加了肺中的β-和γ-ENaC,但仅在暴露> 48 h后才增加,并且对肾脏没有影响。结果表明,肾脏代谢内源性糖皮质激素,而肺代谢。此外,在肺和肾对β-和γ-ENaC表达中的糖皮质激素的反应性之间的显着差异表明,除类固醇外,其他因素可能在调节发育过程中功能性ENaC表达方面也很重要。

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