IP₃ R attenuates oxidative stress and inflammation damage in smoking-induced COPD by promoting autophagy

Tobacco smoking is one of the most important risk factors for chronic obstructive pulmonary disease (COPD). However, the most critical genes and proteins remain poorly understood. Therefore, we aimed to investigate these hub genes and proteins in tobacco smoke-induced COPD, together with the potential mechanism(s). Differentially expressed genes (DEGs) were analysed between smokers and patients with COPD. mRNA expression and protein expression of IP₃ R were confirmed in patients with COPD and extracted smoke solution (ESS)-treated human bronchial epithelial (HBE) cells. Moreover, expression of oxidative stress, inflammatory cytokines and/or autophagy-related protein was tested when IP₃ R was silenced or overexpressed in ESS-treated and/or 3-MA-treated cells. A total of 30 DEGs were obtained between patients with COPD and smoker samples. IP₃ R was identified as one of the key targets in tobacco smoke-induced COPD. In addition, IP₃ R was significantly decreased in patients with COPD and ESS-treated cells. Loss of IP₃ R statistically increased expression of oxidative stress and inflammatory cytokines in ESS-treated HBE cells, and overexpression of IP₃ R reversed the above functions. Furthermore, the autophagy-related proteins (Atg5, LC3 and Beclin1) were statistically decreased, and p62 was increased by silencing of IP₃ R cells, while overexpression of IP₃ R showed contrary results. Additionally, we detected that administration of 3-MA significantly reversed the protective effects of IP₃ R overexpression on ESS-induced oxidative stress and inflammatory injury. Our results suggest that IP₃ R might exert a protective role against ESS-induced oxidative stress and inflammation damage in HBE cells. These protective effects might be associated with promoting autophagy.