Mesenchymal stem cell-derived small extracellular vesicles restored nasal barrier function in allergic rhinitis via miR-143–GSK3B in human nasal epithelial cells
Meiqian Xu PhD , Mei Ren MD , Xinyin Zhang BA , Wenxu Peng BA , Hao Li PhD , Wenjing Liao PhD , Jianlei Xie PhD , Xiaowen Zhang PhD
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引用次数: 0
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–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-induced mouse model to study AR. Both primary and immortalized human nasal epithelial cells (HNEpC) were used to further validate the therapeutic effects of MSC-sEV on epithelial cell function. Then we constructed microRNA (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, 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 glycogen synthase kinase-3β (GSK3B) pathway.
Conclusions
Our results indicated that MSC-sEV mitigated AR and restored nasal epithelial barrier dysfunction through the miR-143–GSK3B axis, which suggested that MSC-sEV have the remarkable ability to treat AR.
期刊介绍:
The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.