T1α, a lung type I cell differentiation gene, is required for normal lung cell proliferation and alveolus formation at birth
T1α, a lung type I cell differentiation gene, is required for normal lung cell proliferation and alveolus formation at birth
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DOI：
10.1016/s0012-1606(02)00098-2
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发表时间：
2003-04-01
影响因子：
2.7
通讯作者：
Williams, MC
中科院分区：
文献类型：
--
作者：
Ramirez, MI;Millien, G;Williams, MC
T1alpha 是肺泡上皮 I 型细胞的分化基因，受发育调节并编码功能未知的顶膜蛋白。 I 型细胞形成气血屏障的形态分化在妊娠的最后几天开始，并持续到出生后。尽管 T1α 在肺芽之前的前肠内胚层中表达，但当表达仅限于肺泡 I 型细胞时，T1α mRNA 和蛋白质水平在晚期胎儿中显着增加。我们生成了 T1alpha 缺失突变小鼠，以研究 T1alpha 在肺发育和分化中的作用，并深入了解其潜在功能。纯合子小鼠在出生时就因呼吸衰竭而死亡，它们的肺部无法膨胀至正常体积。远端肺形态发生改变。在缺乏 T1α 蛋白的情况下，I 型细胞分化受到阻碍，表现为更小的空域、更少的减毒 I 型细胞以及水通道蛋白 5 mRNA 和蛋白（I 型细胞水通道）水平的降低。狭窄的气腔中分泌丰富的表面活性剂、表面活性剂蛋白mRNA的正常水平以及表达表面活性剂蛋白-B的细胞的正常模式和数量表明II型细胞以及肺泡上皮细胞的分化是正常的。出生时间充质和上皮的异常增殖且凋亡细胞数量不变，表明 T1α 的缺失和/或 I 型细胞的异常形态发生改变了远端肺细胞的增殖率，可能是通过上皮-间充质信号传导的破坏。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
T1alpha, a differentiation gene of lung alveolar epithelial type I cells, is developmentally regulated and encodes an apical membrane protein of unknown function. Morphological differentiation of type I cells to form the air-blood barrier starts in the last few days of gestation and continues postnatally. Although T1alpha is expressed in the foregut endoderm before the lung buds, T1alpha mRNA and protein levels increase substantially in late fetuses when expression is restricted to alveolar type I cells. We generated T1alpha null mutant mice to study the role of T1alpha in lung development and differentiation and to gain insight into its potential function. Homozygous null mice die at birth of respiratory failure, and their lungs cannot be inflated to normal volumes. Distal lung morphology is altered. In the absence of T1alpha protein, type I cell differentiation is blocked, as indicated by smaller airspaces, many fewer attenuated type I cells, and reduced levels of aquaporin-5 mRNA and protein, a type I cell water channel. Abundant secreted surfactant in the narrowed airspaces, normal levels of surfactant protein mRNAs, and normal patterns and numbers of cells expressing surfactant protein-B suggest that differentiation of type II cells, also alveolar epithelial cells, is normal. Anomalous proliferation of the mesenchyme and epithelium at birth with unchanged numbers of apoptotic cells suggests that loss of T1alpha and/or abnormal morphogenesis of type I cells alter the proliferation rate of distal lung cells, probably by disruption of epithelial-mesenchymal signaling. (C) 2003 Elsevier Science (USA). All rights reserved.