Transgenic expression of protein phosphatase 2A regulatory subunit B56γ disrupts distal lung differentiation
Transgenic expression of protein phosphatase 2A regulatory subunit B56γ disrupts distal lung differentiation
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DOI：
10.1152/ajplung.00262.2001
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发表时间：
2002-06-01
影响因子：
4.9
通讯作者：
Brautigan, DL
中科院分区：
文献类型：
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作者：
Everett, AD;Kamibayashi, C;Brautigan, DL
发育中的肺远端上皮表现出蛋白磷酸酶2A （PP2A）的高水平表达，这是一种重要的信号酶。在这里，我们报告了在肺中发现，PP2A调节亚基B56gamma在一个离散的发育时期表达，在胚胎日(e) 17时蛋白水平最高，但在新生儿或成人中未检测到蛋白。原位杂交发现，B56gamma在新形成气道远端上皮和间充质细胞中高度表达。b56 γ在支气管上皮和血管平滑肌的表达较低。利用肺特异性表面活性蛋白C （SP-C）启动子转基因表达B56gamma可导致新生儿死亡。SP-C-B56gamma转基因e18胎儿的肺部检查显示近端气道和正常血管，但组织中密集分布着上皮型细胞，缺乏正常的外周肺结构。Wnt信号通路的一个组成部分，β -连环蛋白，在正常肺中受到发育调节，而在B-56gamma转基因胎儿的肺组织中缺失。我们提出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 -连环蛋白信号通路的作用。
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.