Ectopic expression of C/EBPalpha in the lung epithelium disrupts late lung development.
Ectopic expression of C/EBPalpha in the lung epithelium disrupts late lung development.
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肺上皮中 C/EBPα 的异位表达会破坏晚期肺发育。
DOI：
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
M. Nord
中科院分区：
文献类型：
--
作者：
T. Berg;L. Didon;M. Nord
肺从内胚层通过分支形态发生的过程发育。这一过程在肺发育的假腺期高度活跃，并持续到小管期，导致终末囊的形成。CCAAT/增强子结合蛋白（C/EBP）是调节分化和增殖的核心方面的转录因子。我们在这里报告的C/EBPalpha，β和δ在肺的发育表达。C/EBPalpha表现出动态的表达模式，并首次检测到在晚期假腺阶段。在此阶段，在分支小管远端部分的上皮细胞亚群中观察到表达。C/EBPalpha的表达仅限于非增殖细胞。为了研究C/EBPalpha在肺发育中的作用，我们使用人表面活性蛋白C启动子产生了在肺上皮中异位表达C/EBPalpha的转基因小鼠。这些小鼠的肺大小正常，但表现出以更少和更大的发育上皮小管为特征的表型，表明分支过程受到影响。未观察到对总体增殖或细胞分化的影响。当将这种表型与携带Cebpa基因靶向突变的小鼠进行比较时，Cebpa-/-小鼠表现出相似的发育表型。总之，我们的研究结果显示了C/EBPalpha在肺发育中的作用，并表明在肺分支形态发生的后期阶段具有功能。
The lung develops from the endoderm through a process of branching morphogenesis. This process is highly active during the pseudoglandular stage of lung development and continues into the canalicular stage, resulting in the formation of terminal sacs. CCAAT/enhancer binding proteins (C/EBPs) are transcription factors regulating central aspects of differentiation and proliferation. We report here the developmental expression of C/EBPalpha, -beta, and -delta in the lung. C/EBPalpha exhibits a dynamic expression pattern and is first detected during the late pseudoglandular stage. At this stage, expression is observed in a subset of epithelial cells in the distal parts of the branching tubules. The expression of C/EBPalpha is confined to nonproliferating cells. To examine the role of C/EBPalpha in lung development, we generated transgenic mice ectopically expressing C/EBPalpha in the lung epithelium using the human surfactant protein C promoter. Lungs from these mice were of normal size but exhibited a phenotype characterized by fewer and larger developing epithelial tubules, indicating that the branching process was affected. No effects on overall proliferation or cellular differentiation were observed. When this phenotype was compared with that of mice carrying a targeted mutation of the Cebpa gene, the Cebpa-/- mice exhibited a similar developmental phenotype. In conclusion, our results show a role for C/EBPalpha in lung development and suggest a function in the later stages of lung branching morphogenesis.
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DOI：
10.1172/jci16793
发表时间：
2003
期刊：
The Journal of clinical investigation
影响因子：
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作者：
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DOI：
10.1016/s0167-4781(02)00287-7
发表时间：
2002-05
期刊：
Biochimica et biophysica acta
影响因子：
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