Fibroblast growth factor 18 influences proximal programming during lung morphogenesis
Fibroblast growth factor 18 influences proximal programming during lung morphogenesis
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DOI：
10.1074/jbc.m202253200
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发表时间：
2002-06-21
影响因子：
4.8
通讯作者：
Stahlman, MT
中科院分区：
文献类型：
--
作者：
Whitsett, JA;Clark, JC;Stahlman, MT
肺气道的结构和功能沿其长度方向沿着发生显著变化。大直径的传导气道由软骨环和平滑肌组织支撑，并且内衬有参与粘液纤毛清除的纤毛和分泌上皮细胞。在分支形态发生过程中形成的较小的外周气道内衬立方和鳞状细胞，促进气体交换到细毛细血管网络。介导沿着气道长度形成这些变化的细胞类型和结构的因素是未知的。我们在这里报告，成纤维细胞生长因子（FGF）-18在上皮细胞的发育肺的条件表达导致气道采用近端气道的结构特征。外周肺小管数量明显减少，而传导气道的大小和范围增加。在扩张的远端气道壁中发现异常的平滑肌和软骨，并伴有巨大的肺血管。外周肺小管中正常表达的蛋白质（包括SP-B和pro-SP-C）的表达受到抑制。FGF-18 mRNA在正常小鼠肺近端气道软骨周围的基质细胞和外周肺间质中检测到。FGF-18的作用是独特的，因为FGF家族其他成员的表达具有不同的后果。这些数据表明，FGF-18能够在肺形态发生过程中增强近端程序并抑制外周程序。
The structure and functions of the airways of the lung change dramatically along their lengths. Large-diameter conducting airways are supported by cartilaginous rings and smooth muscle tissue and are lined by ciliated and secretory epithelial cells that are involved in mucociliary clearance. Smaller peripheral airways formed during branching morphogenesis are lined by cuboidal and squamous cells that facilitate gas exchange to a network of fine capillaries. The factors that mediate formation of these changing cell types and structures along the length of the airways are unknown. We report here that conditional expression of fibroblast growth factor (FGF)-18 in epithelial cells of the developing lung caused the airway to adopt structural features of proximal airways. Peripheral lung tubules were markedly diminished in numbers, whereas the size and extent of conducting airways were increased. Abnormal smooth muscle and cartilage were found in the walls of expanded distal airways, which were accompanied by atypically large pulmonary blood vessels. Expression of proteins normally expressed in peripheral lung tubules, including SP-B and pro-SP-C, was inhibited. FGF-18 mRNA was detected in normal mouse lung in stromal cells surrounding proximal airway cartilage and in peripheral lung mesenchyme. Effects were unique to FGF-18 because expression of other members of the FGF family had different consequences. These data show that FGF-18 is capable of enhancing proximal and inhibiting peripheral programs during lung morphogenesis.