Cystic Adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung
Cystic Adenomatoid malformations are induced by localized FGF10 overexpression in fetal rat lung
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DOI：
10.1165/rcmb.2007-0290oc
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发表时间：
2008-09-01
影响因子：
6.4
通讯作者：
Flake, Alan W.
中科院分区：
文献类型：
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作者：
Gonzaga, Silvia;Henriques-Coelho, Tiago;Flake, Alan W.
成纤维细胞生长因子-10 (FGF10) 是一种间充质生长因子，参与肺分支形态发生过程中上皮和间充质的相互作用。在目前的工作中，在大鼠肺发育的假腺体或小管阶段，通过经子宫超声引导下实质内显微注射编码 rfgf10 转基因的腺病毒载体，以时间和空间限制的方式短暂诱导 FGF10 过表达。由此产生的畸形的形态学和组织学分类取决于发育阶段和位置。在假腺体阶段，FGF10 的过度表达仅限于近端气管支气管树，导致形成大囊肿，内衬高柱状上皮，主要由 Clara 细胞组成，伴有少量 II 型肺细胞，类似于细支气管型上皮。相反，在小管期，远端肺实质中 FGF10 过度表达导致小囊肿，内衬立方上皮细胞，主要由类似于腺泡上皮分化的 II 型肺细胞组成。 FGF10 过表达诱导的囊性畸形似乎密切再现了人类先天性囊性腺瘤样畸形 (CCAM) 的形态和组织学。这些发现支持 FGF10 在诱导人类 CCAM 中的作用，并为 FGF10 在正常和异常肺发育中的作用提供了进一步的机制见解。
Fibroblast growth factor-10 (FGF10) is a mesenchymal growth factor, involved in epithelial and mesenchymal interactions during lung branching morphogenesis. In the present work, FGF10 overexpression was transiently induced in a temporally and spatially restricted manner, during the pseudoglandular or canalicular stages of rat lung development, by trans-uterine ultrasound-guided intra-parenchymal microinjections of adenoviral vector encoding the rfgf10 transgene. The morphologic and histologic classification of the resulting malformations were dependent upon developmental stage and location. Overexpression of FGF10 restricted to the proximal tracheobronchial tree during the pseudoglandular phase resulted in large cysts lined by tall columnar epithelium composed primarily of Clara cells with a paucity of Type II pneumocytes, resembling bronchiolar type epithelium. In contrast, FGF10 overexpression in the distal lung parenchyma during the canalicular phase resulted in small cysts lined by cuboidal epithelial cells composed of primarily Type II pneumocytes resembling acinar epithelial differentiation. The cystic malformations induced by FGF10 overexpression appear to closely recapitulate the morphology and histology of the spectrum of human congenital cystic adenomatoid malformation (CCAM). These findings support a role for FGF10 in the induction of human CCAM and provide further mechanistic insight into the role of FGF10 in normal and abnormal lung development.