These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: [Regulatory role of Shh signaling pathway in lung development in fetal mice].
    Author: Bao HJ, Ma SD.
    Journal: Nan Fang Yi Ke Da Xue Xue Bao; 2018 Mar 20; 38(3):274-282. PubMed ID: 29643032.
    Abstract:
    OBJECTIVE: To investigate the regulatory role of classical Shh signaling pathway in the development of the epithelium and mesenchyme (bronchial cartilage and smooth muscles) during lung development in fetal mice. METHODS: Immunohistochemical technique was used to detect the expression of Shh signaling pathway receptor Smo and Pdgfr-α in murine fetal lungs to explore the spatial and temporal characteristics of their expression. Based on the interstitial specificity of Pdgfr-α expression, we constructed a Pdgfr-α-cre to establish a E12.5 - E16.5 transgenic mice with specific knockout of the key Shh signaling molecule Smo in the pulmonary interstitium with tamoxifen induction. Immunofluorescence technique was used to observe the epithelium and mesenchyme (bronchial cartilage and smooth muscle) during fetal lung development in the transgenic mice to assess the role of Shh signaling pathway in the epithelial-to-mesenchymal (EMT) transition during the lung development. RESULTS: Smo was highly expressed in the epithelial and stromal lung tissues in the pseudoglandular stage and was gradually lowered over time with its distribution mainly in the interstitial tissues. Pdgfr-α was enriched in the distal lung epithelial and mesenchy tissues in early embryonic lungs and gradually migrated to the proximal stroma until becoming concentrated around the main bronchial proximal stroma. We successfully specific established mouse models of specific mesenchymal Smo knockout. Compared with the control group, the transgenic mice during E12.5-E16.5 showed significantly reduced lung the volume and bronchial branching with also decreased expression of the proximal epithelial P63 (P<0.05). The transgenic mice exhibited alterations in the expression of α-smooth muscle actin with delayed bronchial cartilage development and decreased expression of mucoprotein. CONCLUSION: The temporospatial specific expression of Shh signaling pathway plays an important role in developmental regulation of mouse embryonic lung epithelium and mesenchyme (bronchial cartilage and smooth muscle). 目的: 探讨经典Shh信号通路对小鼠胚胎肺发育过程中上皮、间质（支气管软骨、平滑肌）发育的调控作用。 方法: 利用免疫组化检测Shh通路受体Smo（Smoothened）以及血小板源性生长因子受体（Pdgfr-α）的表达；利用Pdgfr-α间质特异性表达的特点构建Pdgfr-α-cre，通过他莫昔芬的诱导，在E12.5-E16.5（E, embryo）天转基因小鼠肺间质中特异性敲除Shh关键信号分子Smo；利用免疫荧光观察E12.5-E16.5小鼠胚胎肺间质特异性敲除Shh信号通路之后，小鼠胚胎肺发育过程中上皮、间质（支气管软骨、平滑肌）发育的改变，探讨Shh信号通路在小鼠胚胎肺发育过程中对上皮-间质转化的作用。 结果: Smo在假腺期早期的肺上皮与间质中显著表达，后表达量逐渐下调，主要集中在肺间质，Pdgfr-α在假腺期早期胚胎肺中集中在远端肺上皮及间质，后期逐渐往近端间质发展，直至集中在主支气管周围的近端间质；首次利用Pdgfr-α-Cre系统在间质中特异性敲除Smo，成功制备了Smo缺失小鼠模型；与对照组肺相比，E12.5-E16.5基因敲除组小鼠的肺体积缩小，支气管分支形成减少；近端上皮指标P63的表达量下降（P < 0.05）；平滑肌标志物表达水平发生改变；支气管软骨发育滞后，黏蛋白表达量下降。 结论: Shh信号通路的时空特异表达在小鼠胚胎肺上皮、间质（支气管软骨、平滑肌）发育的起着重要的调控作用。
    [Abstract] [Full Text] [Related] [New Search]