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首页> 外文期刊>American Journal of Physiology >Transgenic expression of protein phosphatase 2A regulatory subunit B56gamma disrupts distal lung differentiation.
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Transgenic expression of protein phosphatase 2A regulatory subunit B56gamma disrupts distal lung differentiation.

机译：蛋白磷酸酶2A调节亚基B56gamma的转基因表达破坏了远端肺的分化。

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摘要

The distal epithelium of the developing lung exhibits high-level expression of protein phosphatase 2A (PP2A), a vital signaling enzyme. Here we report the discovery that in the lung, the PP2A regulatory subunit B56gamma is expressed in a discrete developmental period, with the highest protein levels at embryonic day (e) 17, but no detectable protein in the newborn or adult. By in situ hybridization, B56gamma was highly expressed in the distal epithelium of newly forming airways and in mesenchymal cells. In contrast, expression of B56gamma was quite low in the bronchial epithelium and vascular smooth muscle. Transgenic expression of B56gamma using the lung-specific promoter for surfactant protein C (SP-C) resulted in neonatal death. Examination of lungs from SP-C-B56gamma transgenic e18 fetuses revealed proximal airways and normal blood vessels, but the tissue was densely populated with epithelial-type cells and was devoid of normal peripheral lung structure. A component of the Wnt signaling pathway, beta-catenin, was developmentally regulated in the normal lung and was absent in lung tissue from B-56gamma transgenic fetuses. We propose that B56gamma is expressed at a particular stage of lung development to modulate PP2A action on the Wnt/beta-catenin signaling pathway during lung airway morphogenesis.
机译：发育中的肺的远端上皮表现出高水平的蛋白质磷酸酶2A（PP2A）表达，这是一种重要的信号转导酶。在这里，我们报告发现，在肺中，PP2A调节亚基B56gamma在离散的发育时期表达，在胚胎第（e）17天的蛋白质水平最高，但在新生儿或成年人中没有可检测的蛋白质。通过原位杂交，B56γ在新形成的气道的远端上皮和间充质细胞中高表达。相反，B56gamma在支气管上皮和血管平滑肌中的表达非常低。使用针对表面活性剂蛋白C（SP-C）的肺特异性启动子对B56gamma进行转基因表达导致新生儿死亡。从SP-C-B56gamma转基因e18胎儿的肺部检查显示出近端气道和正常血管，但组织中上皮型细胞密集且没有正常的外周肺结构。 Wnt信号通路的一部分，β-catenin，在正常肺中受到发育调节，在B-56gamma转基因胎儿的肺组织中不存在。我们建议B56gamma在肺发育的特定阶段表达，以调节PP2A在肺气道形态发生过程中对Wnt /β-catenin信号通路的作用。

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