SIRT6 inhibits intermittent hypoxia-induced lung injury by stabilizing NRF2.

BACKGROUND

Chronic intermittent hypoxia (CIH) is a typical pathological feature of obstructive sleep apnea (OSA), and CIH can induce lung injury and aggravate the existing lung injury. The inflammatory response, oxidative stress and apoptosis are the key events of CIH-induced lung injury, while Sirtuin 6 (SIRT6) plays a key role in the regulation of biological processes such as inflammation, cell proliferation and oxidative stress. Therefore, this study aimed to further investigate the function of SIRT6 in CIH-induced lung injury.

METHODS

We established CIH-induced rat lung (O2, 5-20.9 %; cycle frequency, 90 s; duration of exposure, 8 h/day for 4weeks) and human bronchial epithelial cells (BEAS-2B) (1 % O2 for 60 min; 21 % O2 for 30 min; 24 h exposure) injury models. The expression of related proteins was detected by ELISA, western blotting, and immunohistochemistry. The damage of lung tissues was detected via Masson staining and HE staining.

RESULTS

This study revealed that the expression of SIRT6 decreased, while inflammatory cytokines IL-6, TNF-α, and IL-1β and cell apoptosis increased, and the level of oxidative stress rose in CIH-induced rat lung tissue and BEAS-2B cells. The overexpression of SIRT6 inhibited the levels of inflammatory cytokines, oxidative stress and apoptosis in CIH-induced rat lung tissue and BEAS-2B cells and relieved the lung injury. Mechanistically, SIRT6 stabilized NRF2 expression via deacetylation to promote NRF2 nuclear translocation and activate HO-1 expression, thereby inhibiting CIH-induced inflammation, oxidative stress and apoptosis and thus alleviating CIH-induced lung injury.

CONCLUSION

Our study revealed that SIRT6 inhibited CIH-induced lung injury through the NRF2/HO-1 signaling axis and that SIRT6 may be a new target for the treatment of CIH-induced lung injury.