Moreno-Barriuso Nuria, López-Malpartida Ana V, de Pablo Flora, Pichel José G
Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas/Universidad de Salamanca, Salamanca, Spain.
Dev Dyn. 2006 Aug;235(8):2040-50. doi: 10.1002/dvdy.20842.
Previous studies on double deficient mice for leukemia inhibitory factor (LIF) and insulin-like growth factor I (IGF-I) reported that they died of respiratory failure, with abnormal lung histology and altered expression of pulmonary markers. Here we analyzed prenatal Lif/Igf-I double mutant mouse embryos to characterize LIF and IGF-I cooperative roles in distal lung epithelium and vascular maturation. Lungs of IGF-I-deficient embryos displayed a higher proportion of type II pneumocytes, less differentiated type I pneumocytes, and failure in alveolar capillary remodeling compared to wild type and LIF-deficient mice. Lif/Igf-I double knockout lungs showed aggravated pulmonary hypoplasia, lower airway volume, increased proliferation, and elevated levels of ERK1/2 activation. In addition, their alveoli were collapsed and lined by type II cells. The differentiation of type I cells barely occurred and capillaries remained in the abundant mesenchyme. These results indicate that LIF collaborates with IGF-I in lung alveolar epithelium and vascular maturation.
先前对白血病抑制因子（LIF）和胰岛素样生长因子I（IGF-I）双缺陷小鼠的研究报告称，它们死于呼吸衰竭，肺部组织学异常，肺部标志物表达改变。在此，我们分析了产前Lif/Igf-I双突变小鼠胚胎，以表征LIF和IGF-I在远端肺上皮和血管成熟中的协同作用。与野生型和LIF缺陷小鼠相比，IGF-I缺陷胚胎的肺显示出更高比例的II型肺细胞、分化程度较低的I型肺细胞，以及肺泡毛细血管重塑失败。Lif/Igf-I双敲除肺表现出更严重的肺发育不全、更低的气道容积、增加的增殖以及ERK1/2激活水平升高。此外，它们的肺泡塌陷，由II型细胞排列。I型细胞几乎不发生分化，毛细血管保留在丰富的间充质中。这些结果表明，LIF与IGF-I在肺泡上皮和血管成熟中协同作用。
