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METHODOLOGY

Ezrin Contributes to the Damage of Airway Epithelial Barrier Related to Diabetes Mellitus

ORCID Icon, , , &
Pages 2609-2621 | Received 12 Nov 2023, Accepted 18 Apr 2024, Published online: 25 Apr 2024
 

Abstract

Background

Diabetes mellitus predisposes individuals to respiratory infections. The airway epithelial barrier provides defense against inhaled antigens and pathogens. Ezrin, is a component of the membrane-cytoskeleton that maintains the cellular morphology, intercellular adhesion, and barrier function of epithelial cells. This study aimed to explore the role of ezrin in airway epithelial barrier damage and correlate its expression and activation with diabetes mellitus.

Methods

This study was performed in a murine model of diabetes mellitus and with human bronchial epithelial BEAS-2B cells using real-time PCR, Western blotting, immunohistochemical and immunofluorescence staining. Ezrin was knocked down in BEAS-2B cells using siRNA. Ezrin phosphorylation levels were measured to determine activation status. The integrity of the airway epithelial barrier was assessed in vivo by characterizing morphological structure, and in vitro in BEAS-2B cells by measuring tight junction protein expression, transepithelial electrical resistance (TER) and permeability.

Results

We demonstrated that ezrin expression levels were lower in the lung tissue and airway epithelium of diabetic mice than those in control mice. The morphological structure of the airway epithelium was altered in diabetic mice. High glucose levels downregulated the expression and distribution of ezrin and connexin 43, reduced the expression of tight junction proteins, and altered the epithelial barrier characteristics of BEAS-2B cells. Ezrin knockdown had effects similar to those of high glucose levels. Moreover, a specific inhibitor of ezrin Thr567 phosphorylation (NSC305787) inhibited epithelial barrier formation.

Conclusion

These results demonstrate that ezrin expression and activation are associated with airway epithelial damage in diabetes mellitus. These findings provide new insights into the molecular pathogenesis of pulmonary infections in diabetes mellitus and may lead to novel therapeutic interventions for airway epithelial barrier damage.

Acknowledgments

We thank Jing Yu for her assistance with cell culture and Linqiang Ma for his assistance with animal experiments.

Disclosure

The authors declare that they have no conflict of interest.

Additional information

Funding

This study was supported by the Scientific and Technological Research Program of the Chongqing Municipal Education Commission (Grant No. KJQN201900428), and Natural Science Foundation of Chongqing (Grant No.CSTB2023NSCQ-MSX0119).