FGF-10 induces SP-C and Bmp4 and regulates proximal-distal patterning in embryonic tracheal epithelium
FGF-10 induces SP-C and Bmp4 and regulates proximal-distal patterning in embryonic tracheal epithelium
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DOI：
10.1152/ajplung.00033.2004
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发表时间：
2004-12-01
影响因子：
4.9
通讯作者：
Shannon, JM
中科院分区：
文献类型：
--
作者：
Hyatt, BA;Shangguan, XF;Shannon, JM
上皮肺芽的诱导、生长和分化受肺上皮及其周围间充质之间信号相互作用的调节。成纤维细胞生长因子-10（FGF-10）表达于远端附近的间充质中，骨形态发生蛋白4（BMP 4）表达于上皮的最远端区域，是肺形态发生中的重要分子。在本研究中，我们使用了两个体外系统来检查肺上皮细胞的诱导，生长和分化。使用Transfilter培养物来确定来自远端肺间充质（LgM）的扩散因子对上皮分支的影响，使用FGF-10珠培养物来确定高局部浓度的单个扩散分子对上皮的影响。胚胎气管上皮细胞（TrE）被诱导生长在两种培养系统中，并表达远端上皮标记表面活性剂蛋白C在最接近的可扩散的蛋白质源的提示。TrE培养的过滤器的相对侧LgM分支的图案类似于完整的肺，而TrE培养的FGF-10珠贴壁类似于一个单一的伸长的上皮芽。BMP 4对肺芽形态发生的作用的检查显示，BMP 4信号传导抑制了两种类型培养物中近端上皮基因Ccsp和Foxj 1的表达，并上调了与FGF-10珠培养的TrE中Sprouty 2的表达。然而，用Noggin拮抗BMP信号传导增加了Ccsp和Foxj 1的表达。
The induction, growth, and differentiation of epithelial lung buds are regulated by the interaction of signals between the lung epithelium and its surrounding mesenchyme. Fibroblast growth factor-10 (FGF-10), which is expressed in the mesenchyme near the distal tips, and bone morphogenetic protein 4 (BMP4), which is expressed in the most distal regions of the epithelium, are important molecules in lung morphogenesis. In the present study, we used two in vitro systems to examine the induction, growth, and differentiation of lung epithelium. Transfilter cultures were used to determine the effect of diffusible factors from the distal lung mesenchyme (LgM) on epithelial branching, and FGF-10 bead cultures were used to ascertain the effect of a high local concentration of a single diffusible molecule on the epithelium. Embryonic tracheal epithelium (TrE) was induced to grow in both culture systems and to express the distal epithelial marker surfactant protein C at the tips nearest the diffusible protein source. TrE cultured on the opposite side of a filter to LgM branched in a pattern resembling intact lungs, whereas TrE cultured in apposition to an FGF-10 bead resembled a single elongating epithelial bud. Examination of the role of BMP4 on lung bud morphogenesis revealed that BMP4 signaling suppressed expression of the proximal epithelial genes Ccsp and Foxj1 in both types of culture and upregulated the expression of Sprouty 2 in TrE cultured with an FGF-10 bead. Antagonizing BMP signaling with Noggin, however, increased expression of both Ccsp and Foxj1.