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

Hongmei Yu,1 Cheng Luo,1 Ru Linghu,2 Juan Yang,3 Haiqiao Wu3 1Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Internal Medicine, Hospital of Chongqing University, Chongqing, People’s Republic of China; 3Department of Respiratory Medicine, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, People’s Republic of ChinaCorrespondence: Hongmei Yu, Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, No. 1, Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +8618996009679, Email yhm920@126.comBackground: 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.Keywords: morphological structure, bronchial epithelial cells, high glucose, tight junction, gap junction