Defects in pulmonary vasculature and perinatal lung hemorrhage in mice heterozygous null for the Forkhead Box f1 transcription factor
Defects in pulmonary vasculature and perinatal lung hemorrhage in mice heterozygous null for the Forkhead Box f1 transcription factor
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DOI：
10.1006/dbio.2001.0322
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发表时间：
2001-07-15
影响因子：
2.7
通讯作者：
Costa, RH
中科院分区：
文献类型：
--
作者：
Kalinichenko, VV;Lim, L;Costa, RH
在55%的Foxf1+/-新生小鼠中，肺组织Forkhead Box F1(Foxf1)转录因子表达降低与致死性肺泡出血有关。肺组织病变的严重程度与Foxf1基因的表达水平有关，正常Foxf1基因表达相对较低的Foxf1+/-小鼠亚群出现肺泡化和血管生成缺陷，肺出血与肺实质肺泡和细支气管区间充质-上皮细胞界面破坏一致，并与细胞凋亡增加和表面活性蛋白B(SP-B)表达减少有关。最后，与Foxf1+/-突变相关的肺缺陷伴随着血管内皮生长因子(VEGF)、血管内皮生长因子受体2(Flk-1)、骨形态发生蛋白4(BMP-4)、短小T盒家族转录因子(Tbx2-Tbx5)和肺Kruppel样因子的表达减少。Foxf1水平的降低导致新生儿肺出血和肺泡形成的异常，提示该转录因子参与了对肺形态发生至关重要的间质-上皮相互作用的调节。(C)2001年学术出版社
Decreased pulmonary expression of Forkhead Box f1 (Foxf1) transcription factor was associated with lethal alveolar hemorrhage in 55% of the Foxf1 +/- newborn mice. The severity of the pulmonary abnormalities correlates with the levels of Foxf1 mRNA, Defects in alveolarization and vasculogenesis were observed in subsets of the Foxf1 +/- mice with relatively low levels of expression from the normal Foxf1 allele, Lung hemorrhage was coincident with disruption of the mesenchymal-epithelial cell interfaces in the alveolar and bronchiolar regions of the lung parenchyma and was associated with increased apoptosis and reduced surfactant protein B (SP-B) expression. Finally, the lung defect associated with the Foxf1 +/- mutation was accompanied by reduced expression of vascular endothelial growth factor (VEGF), the VEGF receptor 2 (Flk-1), bone morphogenetic protein 4 (Bmp-4), and the transcription factors of the Brachyury T-Box family (Tbx2-Tbx5) and Lung Kruppel-like Factor. Reduction in the level of Foxf1 caused neonatal pulmonary hemorrhage and abnormalities in alveologenesis, implicating this transcription factor in the regulation of mesenchyme-epithelial interaction critical for lung morphogenesis. (C) 2001 Academic Press