AHNAK promotes oxidative stress and inflammatory responses in chronic obstructive pulmonary disease by activating the...

Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with high mortality. AHNAK nucleoprotein (AHNAK) is predicted to be highly expressed in COPD; however, its role remains unclear. This study aimed to investigate the role of AHNAK in COPD and the underlying molecular mechanism. A549 cells were treated with cigarette smoke extract (CSE) as an in vitro model, while a COPD mouse model was established using cigarette smoke (CS) exposure and lipopolysaccharide (LPS) on the C57BL/6J mice. Oxidative stress and inflammation were evaluated in cells and serum of mice. The regulation of ANHAK on the Notch pathway was evaluated using Western blot. The results showed that AHNAK was highly expressed in the serum of patients with COPD and CSE-induced A549 cells. Knockdown of AHNAK inhibited oxidative stress and inflammatory responses both in vitro and in vivo, and alleviated lung injury in COPD mice. Additionally, AHNAK knockdown suppressed the activation of the Notch pathway in CSE-induced cells, and activating this pathway reversed the inhibition of oxidative stress and inflammation caused by AHNAK silence. In conclusion, silencing of AHNAK decelerates the progression of COPD by inhibiting oxidative stress and inflammation via the inactivation of the Notch pathway. The findings suggest that targeting AHNAK may be a promising therapeutic strategy for COPD.