Modeling Fibrosis in Three-Dimensional Organoids Reveals New Epithelial Restraints on Fibroblasts

摘要

Epithelial–mesenchymal interactions are critical for organ development, function, and maintenance ( ). In the developing lung, these interactions orchestrate branching morphogenesis during the pseudoglandular stage ( ). The epithelium-derived soluble mediators SHH (sonic hedgehog), BMP4 (bone morphogenetic protein 4), and SPRY2 (sprouty homolog 2) are negative regulators of mesenchymal FGF10 (fibroblast growth factor 10), a key regulator of branching ( ). Many of these developmental pathways are reactivated in fibrotic lung diseases, and most studies have focused on mesenchyme-derived factors that contribute to epithelial disrepair ( , ). However, much less is understood about the epithelial factors that may maintain quiescence of the mesenchyme.