南方医科大学学报2018，Vol.38Issue(3)：274-282,9.DOI:10.3969/j.issn.1673-4254.2018.03.06
Shh信号通路对小鼠胚胎肺发育的调控作用
Regulatory role of Shh signaling pathway in lung development in fetal mice
包和婧 1马树东2
作者信息
- 1. 重庆三峡中心医院肿瘤消化病区,重庆 万州404000
- 2. 南方医科大学南方医院肿瘤科,广东 广州510515
- 折叠
摘要
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).关键词
Shh信号通路/基因敲除/肺发育/免疫荧光Key words
Shh signaling pathway/gene knockdown/lung development/immunofluo-rescence引用本文复制引用
包和婧,马树东..Shh信号通路对小鼠胚胎肺发育的调控作用[J].南方医科大学学报,2018,38(3):274-282,9.
