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首页> 外文期刊>American Journal of Physiology >The role of alpha-, beta-, and gamma-ENaC subunits in distal lung epithelial fluid absorption induced by pulmonary edema fluid.
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The role of alpha-, beta-, and gamma-ENaC subunits in distal lung epithelial fluid absorption induced by pulmonary edema fluid.

机译：α-，β-和γ-ENaC亚基在肺水肿液诱导的远端肺上皮液吸收中的作用。

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摘要

Edema fluid (EF) increases epithelial Na(+) transport by rat fetal distal lung epithelia (FDLE) and induces net lung fluid absorption in fetal mouse lung explants [Rafii B, Gillie DJ, Sulowski C, Hannam V, Cheung T, Otulakowski G, Barker PM, O'Brodovich H. J Physiol (Lond) 544: 537-548, 2002]. We now show that EF increases fluid absorption across monolayers of rat FDLE in a dose-dependent manner. To study the role of subunits of the epithelial Na(+) channel (ENaC) in the phenomena, we cultured explants from the distal lungs of 16-day gestational age wild-type (WT) or alpha-, beta-, or gamma-ENaC knockout or heterozygote (HT) mice. WT explants cultured in media continuously expanded over time as a result of net fluid secretion. In contrast, when explants were exposed to EF for 24 h, net fluid absorption occurred. EF-exposed explants had normal histology, but marked changes were seen after Triton X-100 or staurosporine exposure. Transmission electron microscopy showed EF promoted lamellar body formation and abundant surfactant in the explants' lumens. EF-induced changes in explant size were similar in alpha-ENaC knockout, WT, and HT littermate fetal lung explants (P > 0.05). In contrast, EF's effect was attenuated in beta- and gamma-ENaC knockouts (P < 0.05) vs. WT and HT littermate fetal lung explants. EF exposure slightly decreased or had no effect on mRNA levels for alpha-ENaC in various mouse genotypes but decreased expression of beta- and gamma-ENaC subunit mRNAs (P < 0.01) across all genotype groups. We conclude that beta- and gamma-, but not alpha-, ENaC subunits are essential for EF to exert its maximal effect on net fluid absorption by distal lung epithelia.
机译：水肿液（EF）通过大鼠胎儿远端肺上皮（FDLE）增加上皮Na（+）转运，并诱导胎儿小鼠肺外植体中的净肺液吸收[Rafii B，Gillie DJ，Sulowski C，Hannam V，Cheung T，Otulakowski G ，Barker PM，O'Brodovich H.J Physiol（Lond）544：537-548，2002]。我们现在显示，EF以剂量依赖的方式增加了大鼠FDLE单层的液体吸收。为了研究上皮Na（+）通道（ENaC）的亚基在这种现象中的作用，我们培养了16天胎龄野生型（WT）或α-，β-或gamma- ENaC基因敲除或杂合子（HT）小鼠。由于净液体分泌，在培养基中培养的野生型外植体随着时间不断扩大。相反，当外植体暴露于EF 24 h时，发生了净液体吸收。暴露于EF的外植体组织学正常，但在Triton X-100或星形孢菌素暴露后，观察到明显变化。透射电子显微镜显示，EF促进了外植体腔中的层状体形成和丰富的表面活性剂。 EF诱导的外植体大小变化在α-ENaC基因敲除，WT和HT同窝胎儿肺外植体中相似（P> 0.05）。相反，与WT和HT同窝胎儿肺外植体相比，在β-和γ-ENaC基因敲除中，EF的作用减弱（P <0.05）。 EF暴露在各种小鼠基因型中对α-ENaC的mRNA水平略有降低或没有影响，但在所有基因型组中，β-和γ-ENaC亚基mRNA的表达均降低了（P <0.01）。我们得出结论，β-和γ-而不是α-的ENaC亚基对于EF发挥其最大作用，对远端肺上皮细胞的净液体吸收具有最大作用。

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