MOTS-c attenuates airway barrier dysfunction in allergic asthma by inhibiting epithelial apoptosis via Nrf2 pathway.

BACKGROUND

Allergic asthma (AA), a severe chronic respiratory disease of chronic airway inflammation, is characterized by bronchial epithelial barrier dysfunction. The MOTS-c/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a protective role in various diseases by reducing inflammatory responses. This study aimed to evaluate the effects of MOTS-c on airway epithelial barrier function in AA.

METHODS

MOTS-c levels in the serum of patients with asthma and healthy volunteers were measured by ELISA. C57BL/6 and Nrf2-knockout (Nrf2) mice were stimulated with house dust mites (HDM) to establish an asthma model. Lung tissue injury and mitochondrial function were assessed using hematoxylin and eosin, immunofluorescence, and immunohistochemistry staining. BEAS-2B cells were pretreated using 10 μM MOTS-c for 2 h and then treated with HDM (1 μM) for 24 h. The epithelial barrier and mitochondrial function were detected through western blot and real-time quantitative polymerase chain reaction, respectively.

RESULTS

MOTS-c levels were lower in the serum of patients with asthma than in that of healthy volunteers. Exogenous supplementation of MOTS-c significantly ameliorated lung tissue damage, inflammation, and oxidative stress caused by HDM. However, MOTS-c reversed the barrier function and mitochondrial damage in AA mice. Furthermore, MOTS-c significantly inhibited inflammation, oxidative stress, and mitochondrial damage in HDM-stimulated BEAS-2B cells. Mechanistically, MOTS-c attenuates airway barrier damage in AA by inhibiting bronchial epithelial apoptosis via the Nrf2 pathway.

CONCLUSION

MOTS-c alleviated AA by attenuating airway barrier dysfunction through an Nrf2-dependent mechanism. Therefore, MOTS-c may potentially act as a novel protective agent against AA.