Effects of fibroblasts-derived exosomal FAP in regulating EMT in epithelial cells from chronic rhinosinusitis

Objectives: Exosomes play a crucial role in intercellular communication and may contribute to the development of various diseases. Nevertheless, their role in Nasal Polyps (NPs) remains poorly understood. Herein, Nasal Polyp Fibroblasts (NPF) were used to release exosomes, and epithelial cells were cocultured with NPF-derived exosomes to analyze Epithelial-Mesenchymal Transition (EMT) in Chronic Rhinosinusitis (CRS).

Methods: We obtained exosomes from the culture media of NPFs treated with or without Fibroblast Activation Protein (FAP) inhibitor-4. Epithelial cells were coincubated with NPF-derived exosomes, and exosome internalization was analyzed by confocal microscopy. FAP and EMT markers in epithelial cells were detected by Western blotting and RT-PCR, while the migration ability of epithelial cells was detected by scratch experiments.

Results: NPF-derived FAP-containing exosomes were rapidly internalized by nasal epithelial cells. These exosomes induced epithelial cells to express reduced E-cadherin and increased N-Cadherin and vimentin levels, while FAPI-4 could reverse these changes. Furthermore, the migration ability of epithelial cells was enhanced by FAP-carrying exosomes. Our results reveal that FAP-containing exosomes promote EMT in epithelial cells.

Conclusion: NPF-derived FAP-containing exosomes mediate the interaction between epithelial cells and fibroblasts and induce the EMT of epithelial cells, thereby potentially playing a crucial role in promoting remodeling in CRS. These findings suggest that FAP is a potential therapeutic target for the treatment of CRS patients.

Level of evidence: Level 3 ‒ Non-randomized controlled cohort/follow-up study Recommendation B.

Chronic rhinosinusitis; Epithelial cells; Epithelial mesenchymal transition; Exosome; Fibroblast activation protein.