MicroRNA-155 differentially regulates IL-13Rα1 and IL-13Rα2 expression and signaling that drives abnormal epithelial cells functions in severe asthma - 20/03/24
Resumen |
Rationale |
Asthma is a chronic airway disease characterized by a prevailing type 2 inflammation and airway remodeling. In asthma, microRNA-155 (miR-155) is known to increase in innate and adaptive immune cells and is associated with disease severity. However, little is known about its role in lung structural cells.
Objectives |
This study investigated the expression of miR-155 and its regulatory role on IL-13 receptors and function in bronchial epithelial cells (BEC) isolated from healthy and severe asthmatic donors.
Methods |
BECs isolated from healthy donors and severe asthma patients were stimulated with IL-13. MiR-155 expression and release were measured by RT-PCR in BECs and in their derived exosomes. Modulation of miR-155 in BECs was performed using transfection of miR-155 inhibitor and miR-155 mimic. MUC5AC, IL-8 and EOTAXIN-1 expression were measured by RT-PCR and BECs repair process was assessed by wound healing assay. IL-13Rα1 and IL-13Rα2 expression and downstream pathways were evaluated by western blot.
Main results |
Severe asthma BECs showed an increased expression and exosomal release of miR-155 at baseline and amplified following IL-13 stimulation. Additionally, they expressed more IL-13Rα1 and less IL-13Rα2 than healthy BECs. IL-13Rα1 but not IL-13Rα2 induced miR-155 expression. Following miR-155 overexpression, BECs expressed more MUC5AC, IL-8 and EOTAXIN-1 through IL-13Rα1/SOCS1/STAT6 pathway and harbored a delayed repair process with a downregulated IL-13α2/ERK1/2/c-Jun signaling.
Conclusions |
MiR-155 is overexpressed in severe asthma BECs and contributes to modulate IL-13Rα1 and IL-13Rα2 expression favoring mucin and eosinophils recruitment to detriment of airway repair. These results contribute to a better understanding of miR-155 role in the abnormal behavior of severe asthma BECs.
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Vol 41 - N° 3
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