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首页> 外文期刊>American Journal of Physiology >Antisense inhibition of surfactant protein A decreases tubular myelin formation in human fetal lung in vitro.
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Antisense inhibition of surfactant protein A decreases tubular myelin formation in human fetal lung in vitro.

机译：表面活性剂蛋白A的反义抑制可减少体外人胎肺中肾小管髓磷脂的形成。

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摘要

Surfactant protein A (SP-A) is the most abundant of the surfactant-associated proteins. SP-A is involved in the formation of tubular myelin, the modulation of the surface tension-reducing properties of surfactant phospholipids, the metabolism of surfactant phospholipids, and local pulmonary host defense. We hypothesized that elimination of SP-A would alter the regulation of SP-B gene expression and the formation of tubular myelin. Midtrimester human fetal lung explants were cultured for 3-5 days in the presence or absence of an antisense 18-mer phosphorothioate oligonucleotide (ON) complementary to SP-A mRNA. After 3 days in culture, SP-A mRNA was undetectable in antisense ON-treated explants. After 5 days in culture, levels of SP-A protein were also decreased by antisense treatment. SP-B mRNA levels were not affected by the antisense SP-A ON treatment. However, there was decreased tubular myelin formation in the antisense SP-A ON-treated tissue. We conclude that selective elimination of SP-A mRNA and protein results in a decrease in tubular myelin formation in human fetal lung without affecting SP-B mRNA. We speculate that SP-A is critical to the formation of tubular myelin during human lung development and that the regulation of SP-B gene expression is independent of SP-A gene expression.
机译：表面活性剂蛋白A（SP-A）是与表面活性剂相关的蛋白中含量最高的蛋白。 SP-A参与管状髓磷脂的形成，表面活性剂磷脂表面张力降低特性的调节，表面活性剂磷脂的代谢和局部肺宿主防御。我们假设消除SP-A将改变SP-B基因表达的调节和肾小管髓磷脂的形成。在存在或不存在与SP-A mRNA互补的反义18-mer硫代磷酸酯寡核苷酸（ON）的情况下，将中孕期人胎儿肺外植体培养3-5天。培养3天后，在反义ON处理的外植体中未检测到SP-A mRNA。培养5天后，通过反义处理也降低了SP-A蛋白的水平。 SP-B mRNA水平不受反义SP-A ON处理的影响。但是，在反义SP-A ON处理的组织中肾小管髓磷脂形成减少。我们得出的结论是，选择性消除SP-A mRNA和蛋白质会导致人胎肺中肾小管髓磷脂形成的减少，而不会影响SP-B mRNA。我们推测，SP-A对人肺发育过程中肾小管髓鞘的形成至关重要，并且SP-B基因表达的调控独立于SP-A基因表达。

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