Mesenchymal stem cell-derived small extracellular vesicles restored nasal barrier function in allergic rhinitis via miR-143-GSK3β in human nasal epithelial cells.

Abstract

Background: The nasal epithelial barrier is the first line of defense against the deep entry of pathogens or aeroallergens, and is more critical in allergic rhinitis (AR). Restoring epithelial barrier dysfunction might be a promising strategy for AR. Recent studies reported that mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEV) potentially inhibit the inflammation response and promote tissue regeneration. However, their effect on nasal epithelial cells remains unknown.

Objectives: This study sought to describe the therapeutic effect of MSC-sEV on AR, particularly focusing their effect on nasal epithelial cells and underlying molecular mechanisms.

Methods: We utilized an ovalbumin (OVA)-induced mouse model to study AR. Both primary and immortalized human nasal epithelial cells were used to further validate the therapeutic effects of MSC-sEV on epithelial cell function. Then we constructed miR-143 overexpressing and low-expressing HNEpC and MSC-sEV to elucidate molecular mechanisms. Transcriptome analysis was performed to identify the downstream pathways involved.

Results: MSC-sEV successfully maintained nasal barrier integrity in AR mouse model. The MSC-sEV therapeutic effect on the nasal barrier was substantiated in HNEpC. Mechanistically, microRNA (miR)-143 was a candidate mediator of the above effects. Subsequently, transfecting HNEpC with miR-143 partially mimicked the restoring effect of MSC-sEV. MSC-sEV overexpressing miR-143 exerted more therapeutic effects on tight junctions and barrier integrity. Moreover, miR-143 regulated the GSK3β pathway.

Conclusions: Our results indicated that MSC-sEV mitigated AR and restored nasal epithelial barrier dysfunction through the miR-143-GSK3β axis, which suggested that MSC-sEV have the remarkable ability to treat AR.