The mouse forkhead gene Foxp2 modulates expression of the lung genes.
The mouse forkhead gene Foxp2 modulates expression of the lung genes.
复制标题
DOI：
10.1016/j.lfs.2010.05.009
复制
发表时间：
2010-07
期刊：
影响因子：
6.1
通讯作者：
Zhi Yang;Keisuke Hikosaka;M. Sharkar;T. Tamakoshi;Abhishek Chandra;Bo Wang-;Tatsuo Itakura;Xiaodong Xue;T. Uezato;Wataru Kimura;N. Miura
中科院分区：
文献类型：
--
作者：
Zhi Yang;Keisuke Hikosaka;M. Sharkar;T. Tamakoshi;Abhishek Chandra;Bo Wang-;Tatsuo Itakura;Xiaodong Xue;T. Uezato;Wataru Kimura;N. Miura
AIMSFoxp2在小鼠发育期间在肺中表达。产生单克隆抗小鼠Foxp2抗体以确定发育中的肺中的表达模式。接下来，在H441和A549细胞中研究了Foxp2对两个肺基因CC10和表面活性蛋白C（SPC）基因的转录控制。第三，比较Foxp2和Foxf2在发育中肺中的表达模式。最后，方法采用免疫组织化学染色和原位杂交技术，对Foxf2基因敲除小鼠的肺组织进行原位杂交，观察Foxf2基因敲除小鼠肺组织中Foxp2的表达情况。Foxp2抗体证实，Foxp2在E10.5时在支气管上皮中表达，并且其表达变得限于伸长的细支气管上皮的远端部分，并且最终限于II型肺泡上皮出生前后和成年时的细胞。Foxp2在Nkx2.1存在下激活A549细胞中SPC基因启动子，而在H441细胞中抑制CC10基因启动子。接下来，发现Foxp2和Foxf2的表达结构域在肺中是排他性的。最后，Foxp2的表达在Foxf2基因敲除小鼠的肺中没有改变。意义Foxp2蛋白在气道上皮生长的远端边缘表达。当细支气管伸长时，Foxp2抑制CC10表达。当肺泡形成时，Foxp2调节II型肺泡细胞中Nkx2.1介导的SPC表达。Foxp2和Foxf2分别在肺泡和间充质中独立地发挥不同的作用。
AIMSFoxp2 is expressed in the lung during mouse development. A monoclonal anti-mouse Foxp2 antibody was created to determine the expression pattern in the developing lung. Next, transcriptional control of two lung genes, CC10 and surfactant protein C (SPC) genes, by Foxp2 was investigated in H441 and A549 cells. Thirdly, expression patterns of Foxp2 and Foxf2 were compared in the developing lung. Finally, Foxp2 expression was determined in the Foxf2-null mice.MAIN METHODSImmunohistochemical staining and in situ hybridization were applied to the sections of lungs in the developing embryos.KEY FINDINGSMonoclonal anti-Foxp2 antibody demonstrated that Foxp2 was expressed in the bronchial epithelium at E10.5 and its expression became restricted to the distal portion of the elongating bronchiolar epithelium and finally to type II alveolar epithelial cells around birth and in the adult. Foxp2 activated the SPC gene promoter in the presence of Nkx2.1 in A549 cells while it repressed the CC10 gene promoter in H441 cells. Next, the expression domains of the Foxp2 and Foxf2 were found to be exclusive in the lung. Finally, the expression of Foxp2 did not change in the lung of Foxf2-null mice.SIGNIFICANCEThe Foxp2 protein is expressed in the growing distal edge of airway epithelium. When the bronchiolus elongates, Foxp2 suppresses CC10 expression. When the lung alveolus is formed, Foxp2 modulates the Nkx2.1-mediated SPC expression in type II alveolar cells. Foxp2 and Foxf2 independently play distinct roles in the alveoli and the mesenchyme, respectively.