Abstract
Rationale: Lung development with its key processes alveolarization, angiogenesis, airway branching and underlying matrix scaffold formation critically depends on the cross-talk between different cell-types. Neonatal alveolar cell-derived organoids can recapitulate lung architacture and functional changes during lung development. Cellular and molecular behavior study in this model can provide information on cell type specific crosstalk among fibroblasts and epithelial progenitors-derived cells. The ex vivo model is amenable to specific pathways modulation and therefore can provide insight into the interaction with other known pathways and indicate potential therapeutic targets for neonatal lung diseases. This study investigated the role of receptor tyrosine kinases 3 (ERBB3) pathway in the interplay of fibroblast-epithelial cells when forming 3D structure that simulates alveolarization.
Methods: Neonatal lung organoids were generated with mouse lung fibroblasts(CCL206) and primary lung epithelial cells (CD45-/CD31-) from neonatal C57BL/6 mice of postnatal day 7, and then incubated with Neuregulin (NRG), the ligand activating ERBB3 receptor. Organoid number and size were measured and compared to adult, and Erbb3 signaling was assessed with quantitative immunofluorescence and gene expression analyses.
Results: Neonatal lung organoids has higher colony forming efficiency comparing to adult ones. Higher amount of fibroblasts accelerates the formation and segmentation of the organoids. The NRG treatment increased the expression and phosphorylation of Erbb3,and promoted the segmentation of neonatal organoids.
Conclusion: Erbb3 pathway plays an important role driving alveolar structure formation.
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, OA1619.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021