Elf5 is an epithelium-specific, fibroblast growth factor-sensitive transcription factor in the embryonic lung
Elf5 is an epithelium-specific, fibroblast growth factor-sensitive transcription factor in the embryonic lung
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Elf5 是胚胎肺上皮特异性的成纤维细胞生长因子敏感转录因子
DOI：
10.1002/dvdy.21133
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发表时间：
2007-05-01
影响因子：
2.5
通讯作者：
Shannon, John M.
中科院分区：
文献类型：
--
作者：
Metzger, David E.;Xu, Yan;Shannon, John M.
成纤维细胞生长因子（FGF）信号传导已被证明对正常肺发育的许多方面至关重要。为了确定FGF信号传导的上皮靶点，我们在胚胎期(E) 11.5天的小鼠肺中培养了24小时，无论是否存在抑制分支形态发生的FGF受体拮抗剂SU5402。Affymetrix基因芯片分析处理和对照上皮发现了几个受FGF信号调节的基因，包括Elf5，上皮特异性Ets转录因子家族的成员。SU5402在无间质培养的E12.5上皮中降低Elf5的表达，表明其抑制作用是直接的。原位杂交显示Elf5在肺发育过程中具有动态表达模式。我们发现Elf5的表达是由FGF7和FGF10诱导的，FGF7和FGF10是主要结合FGFR2b的配体。为了进一步确定FGF激活Elf5表达的途径，我们在E11.5肺尖中培养了抑制FGF受体（SU5402）、pi3 -激酶/ akt介导的信号传导（LY294002）和NLAP激酶/ erk介导的信号传导（UO126）的化合物。我们发现SU5402和LY294002显著降低Elf5的表达，而U0126没有影响。LY294002也降低了纯化上皮培养中Elf5的表达。最后，在E17.5肺近端上皮气道中，pAkt与Elf5共表达。这些结果表明，Elf5是肺中FGF敏感的转录因子，具有动态表达模式，FGF通过PI3-Kinase/Akt通路通过FGFR2b调控Elf5。生态学报，2009,32(6):1175-1192。(C) 2007 Wiley-Liss, Inc。
Fibroblast growth factor (FGF) signaling has been shown to be essential for many aspects of normal lung development. To determine epithelial targets of FGF signaling, we cultured embryonic day (E) 11.5 mouse lungs for 24 hr in the presence or absence of the FGF receptor antagonist SU5402, which inhibited branching morphogenesis. Affymetrix gene chip analysis of treated and control epithelia identified several genes regulated by FGF signaling, including Elf5, a member of the Epithelial-specific Ets family of transcription factors. SU5402 reduced Elf5 expression in mesenchyme-free cultures of E12.5 epithelium, demonstrating that the inhibition was direct. In situ hybridization revealed that Elf5 had a dynamic pattern of expression during lung development. We found that expression of Elf5 was induced by FGF7 and FGF10, ligands that primarily bind FGFR2b. To further define the pathways by which FGFs activate Elf5 expression, we cultured E11.5 lung tips in the presence of compounds to inhibit FGF receptors (SU5402), PI3-Kinase/Akt-mediated signaling (LY294002), and NLAP Kinase/Erk-mediated signaling (UO126). We found that SU5402 and LY294002 significantly reduced Elf5 expression, whereas U0126 had no effect. LY294002 also reduced Elf5 expression in cultures of purified epithelium. Finally, pAkt was coexpressed with Elf5 in the proximal epithelial airways of E17.5 lungs. These results demonstrate that Elf5 is an FGF-sensitive transcription factor in the lung with a dynamic pattern of expression and that FGF regulation of Elf5 by means of FGFR2b occurs through the PI3-Kinase/Akt pathway. Developmental Dynamics 236.1175-1192, 2007. (C) 2007 Wiley-Liss, Inc.