The EphA1 and EphA2 Signaling Modulates the Epithelial Permeability in Human Sinonasal Epithelial Cells and the Rhinovirus Infection Induces Epithelial Barrier Dysfunction via EphA2 Receptor Signaling

Deficiencies in epithelial barrier integrity are involved in the pathogenesis of chronic rhinosinusitis (CRS). This study aimed to investigate the role of ephrinA1/ephA2 signaling on sinonasal epithelial permeability and rhinovirus-induced epithelial permeability. This role in the process of epithel...

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Published in:International journal of molecular sciences 2023-02, Vol.24 (4), p.3629
Main Authors: Shin, Jae Min, Han, Moon Soo, Park, Jae Hyung, Lee, Seung Hyeok, Kim, Tae Hoon, Lee, Sang Hag
Format: Article
Language:English
Subjects:
Cell Membrane Permeability - genetics
Cell Membrane Permeability - physiology
chronic rhinosinusitis
Development and progression
EphA2 protein
ephrinA1
ephrinA2 receptor
epithelial barrier
Epithelial cells
Epithelial Cells - metabolism
Epithelial Cells - physiology
Epithelium
Health aspects
Humans
Infection
Infections
Inhibitors
Kinases
Microscopy
Paranasal sinus
Pathogens
Permeability
Picornaviridae Infections - metabolism
Proteins
Receptor, EphA1
Receptor, EphA2 - metabolism
Rhinitis
Rhinosinusitis
Rhinovirus
Rhinovirus - pathogenicity
RNA, Double-Stranded
RNA, Small Interfering - metabolism
Signal Transduction - physiology
Sinusitis
siRNA
Surgery
Tobacco smoke
Viral infections
Zonula occludens-1 protein
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Summary:Deficiencies in epithelial barrier integrity are involved in the pathogenesis of chronic rhinosinusitis (CRS). This study aimed to investigate the role of ephrinA1/ephA2 signaling on sinonasal epithelial permeability and rhinovirus-induced epithelial permeability. This role in the process of epithelial permeability was evaluated by stimulating ephA2 with ephrinA1 and inactivating ephA2 with ephA2 siRNA or inhibitor in cells exposed to rhinovirus infection. EphrinA1 treatment increased epithelial permeability, which was associated with decreased expression of ZO-1, ZO-2, and occludin. These effects of ephrinA1 were attenuated by blocking the action of ephA2 with ephA2 siRNA or inhibitor. Furthermore, rhinovirus infection upregulated the expression levels of ephrinA1 and ephA2, increasing epithelial permeability, which was suppressed in ephA2-deficient cells. These results suggest a novel role of ephrinA1/ephA2 signaling in epithelial barrier integrity in the sinonasal epithelium, suggesting their participation in rhinovirus-induced epithelial dysfunction.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms24043629