C/EBPα is required for lung maturation at birth
C/EBPα is required for lung maturation at birth
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DOI：
10.1242/dev.02273
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发表时间：
2006-03-15
期刊：
影响因子：
4.6
通讯作者：
Ikegami, M
中科院分区：
文献类型：
--
作者：
Martis, PC;Whitsett, JA;Ikegami, M
肺周围的上皮细胞合成肺表面活性剂，降低气液界面的表面张力。肺部缺乏表面活性剂脂质和蛋白质会导致呼吸窘迫综合征，这是早产儿发病和死亡的常见原因。我们发现，C/EBP α 在妊娠晚期呼吸道上皮的成熟中起着至关重要的作用，是产生肺功能所需的表面活性剂脂质和蛋白质所必需的。胎儿小鼠呼吸道上皮细胞中 Cebpa 基因的缺失导致出生时呼吸衰竭。肺的结构和生化成熟被延迟。表面活性剂脂质和蛋白质（包括 SP-A、SP-B、SP-C、SP-D、ABCA3（层状体相关蛋白）和 FAS（脂肪酸合成前体））的正常合成取决于呼吸道上皮细胞中 C/EBP α 的表达。 Cebpa 基因的缺失导致 Tgfb2 表达增加，Tgfb2 是一种抑制肺上皮细胞增殖和分化的生长因子。 C/EBP α 的正常表达需要 Titf1 和 Foxa2，这些转录因子在围产期肺分化中也发挥着重要作用。 C/EBP α 参与转录网络，该网络是调节介导围产期肺成熟和表面活性剂稳态的基因所需的，而表面活性剂稳态是适应出生时空气呼吸所必需的。
Epithelial cells lining the peripheral lung synthesize pulmonary surfactant that reduces surface tension at the air-liquid interface. Lack of surfactant lipids and proteins in the lungs causes respiratory distress syndrome, a common cause of morbidity and mortality in preterm infants. We show that C/EBP alpha plays a crucial role in the maturation of the respiratory epithelium in late gestation, being required for the production of surfactant lipids and proteins necessary for lung function. Deletion of the Cebpa gene in respiratory epithelial cells in fetal mice caused respiratory failure at birth. Structural and biochemical maturation of the lung was delayed. Normal synthesis of surfactant lipids and proteins, including SP-A, SP-B, SP-C, SP-D, ABCA3 (a lamellar body associated protein) and FAS (precursor of fatty acid synthesis) were dependent upon expression of the C/EBP alpha in respiratory epithelial cells. Deletion of the Cebpa gene caused increased expression of Tgfb2, a growth factor that inhibits lung epithelial cell proliferation and differentiation. Normal expression of C/EBP alpha required Titf1 and Foxa2, transcription factors that also play an important role in perinatal lung differentiation. C/EBP alpha participates in a transcriptional network that is required for the regulation of genes mediating perinatal lung maturation and surfactant homeostasis that is necessary for adaptation to air breathing at birth.