- Meeting abstract
- Open Access
Impact of embryonic Fgf10 expression deficiency on embryonic mouse lung development and repair following hyperoxia injury
© Chao et al. 2015
Published: 1 July 2015
Bronchopulmonary dysplasia (BPD), a chronic lung disease of preterm infants, is characterized by impaired alveolar growth and pathologic vascularization.
To investigate the impact of Fgf10 expression deficiency on embryonic lung development and hyperoxia lung injury (BPD mouse model).
Embryonic lungs (Fgf10 +/- and Fgf10 +/+ [WT]) were harvested at E12.5 and E18.5. Lung branches were quantified and H&E staining was performed.
After BrdU labeling lungs were harvest from embryos at E12.5. BrdU staining was performed on paraffin-embedded sections.
Transcriptomic analyses were performed by using whole lung RNA isolated at E18.5.
BPD mouse model:
Fgf10 +/- and Fgf10 +/+ mice were exposed to 85% O2 from P0-P8. Lung morphometric analysis, IHC staining (α-Actin/vWF staining, SPC, E-cadherin, Ki67, TUNEL), gene expression analysis (RNA isolated from type II alveolar epithelial cells [AEC II]), FACS (epithelial/ mesenchymal progenitor cells, AEC I/ II) were performed at P3.
Embryonic Fgf10 heterozygous lungs exhibit epithelial branching defects and decreased Fibroblast growth factor signaling.
Embryonic Fgf10 +/- lungs show decreased epithelial proliferation.
Lungs of E18.5 Fgf10 +/- embryos display structural defects and abnormal gene expression.
Fgf10 heterozygous pups display increased sensitivity to hyperoxia exposure associated with significant structural lung defects. Transcriptomic analyses show epithelial defects linked to cell cycle dysregulation and increased Tgfb signaling. Fgf10 heterozygous vessels are more sensitive to hyperoxia injury and exhibit a less muscularized phenotype. SPC staining shows significant decrease in SPC+ cells after hyperoxia injury. FACS analysis revealed an increase of AEC I on the expenses of AEC II (progenitor cell).
Fgf10 deficiency leads to impaired embryonic lung development and death upon postnatal hyperoxia lung injury due to vulnerability of the epithelium.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.