Mesenchymal maintenance of distal epithelial cell phenotype during late fetal lung development
Mesenchymal maintenance of distal epithelial cell phenotype during late fetal lung development
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DOI：
10.1152/ajplung.00221.2006
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发表时间：
2007-03-01
影响因子：
4.9
通讯作者：
Post, Martin
中科院分区：
文献类型：
--
作者：
Deimling, Julie;Thompson, Kate;Post, Martin
经典的组织重组实验已经报道，在妊娠早期，气管和远端肺上皮都具有对间充质信号作出反应的可塑性。在此，我们研究了上皮-间充质相互作用在维持上皮细胞分化在晚期（E19-E21，任期= 22天）的大鼠胎儿妊娠的作用。将分离的远端肺上皮细胞与来自肺、皮肤和肠的间充质细胞重组，并将同型或异型重组细胞聚集体培养长达5天。用不同来源的间充质包埋肺上皮细胞诱导了一种特异于诱导间充质类型的形态学模式。原位分析表面活性蛋白（SP）-C，SP-B，和克拉拉细胞分泌蛋白（CCSP）的表达，以及SP-C和CCSP启动子反式激活实验，发现远端肺上皮细胞需要肺间充质维持肺泡，但不是细支气管，表型。用抗FGF7抗体孵育肺重组体导致间充质诱导的SP-C启动子反式激活的部分抑制。调节细胞分化的Notch途径的组分Delta和Lunatic fringe的免疫反应性在异型重组体中下调。相反，Hes1 mRNA表达在这些重组体中增加。累积起来，这些结果表明，在胎儿妊娠晚期，远端肺上皮细胞并不完全致力于一个特定的表型，仍然有可塑性，以响应各种信号。它们的肺泡表型可能通过Notch/Notch配体相互作用和间充质因子（包括FGF7）维持。
Classical tissue recombination experiments have reported that at early gestation both tracheal and distal lung epithelium have the plasticity to respond to mesenchymal signals. Herein we examined the role of epithelial-mesenchymal interactions in maintaining epithelial differentiation at late (E19-E21, term = 22 days) fetal gestation in the rat. Isolated distal lung epithelial cells were recombined with mesenchymal cells from lung, skin, and intestine, and the homotypic or heterotypic recombinant cell aggregates were cultured for up to 5 days. Recombining lung epithelial cells with mesenchyme from various sources induced a morphological pattern that was specific to the type of inducing mesenchyme. In situ analysis of surfactant protein (SP)-C, SP-B, and Clara cell secretory protein (CCSP) expression, as well as SP-C and CCSP promoter transactivation experiments, revealed that distal lung epithelium requires lung mesenchyme to maintain the alveolar, but not bronchiolar, phenotype. Incubation of lung recombinants with an anti-FGF7 antibody resulted in a partial inhibition of mesenchyme-induced SP-C promoter transactivation. Immunoreactivity for Delta and Lunatic fringe, components of the Notch pathway that regulates cell differentiation, was downregulated in the heterotypic recombinants. In contrast, Hes1 mRNA expression was increased in these recombinants. Cumulatively, these results suggest that at late fetal gestation, distal lung epithelial cells are not fully committed to a specific phenotype and still have the plasticity to respond to various signals. Their alveolar phenotype is likely maintained by Notch/Notch ligand interactions and mesenchymal factors, including FGF7.