Peroxinredoxin 6 reduction accelerates cigarette smoke extract-induced senescence by regulating autophagy in BEAS-2B cells

Cigarette smoke (CS)-induced accelerated senescence and insufficient autophagy has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Peroxiredoxin (PRDX) 6 is a protein with prevalent antioxidant capacity. Previous studies indicate that PRDX6 could activate autophagy and alleviate senescence in other diseases. The present study investigated whether PRDX6-regulated autophagy was involved in the regulation of CS extract (CSE)-induced BEAS-2B cell senescence via the knockdown of PRDX6 expression. Furthermore, the present study evaluated the mRNA levels of PRDX6, autophagy and senescence-associated genes in the small airway epithelium from patients with COPD by analyzing the GSE20257 dataset from the Gene Expression Omnibus database. The results demonstrated that CSE reduced PRDX6 expression levels and transiently induced the activation of autophagy, followed by the accelerated senescence of BEAS-2B cells. Knockdown of PRDX6 induced autophagy degradation and accelerated senescence in CSE-treated BEAS-2B cells. Furthermore, autophagy inhibition by 3-Methyladenine increased P16 and P21 expression levels, while autophagy activation by rapamycin reduced P16 and P21 expression levels in CSE-treated BEAS-2B cells. The GSE20257 dataset revealed that patients with COPD had lower PRDX6, sirtuin (SIRT) 1 and SIRT6 mRNA levels, and higher P62 and P16 mRNA levels compared with non-smokers. P62 mRNA was significantly correlated with P16, P21 and SIRT1, which indicated that insufficient autophagic clearance of damaged proteins could be involved in accelerated cell senescence in COPD. In conclusion, the present study demonstrated a novel protective role for PRDX6 in COPD. Furthermore, a reduction in PRDX6 could accelerate senescence by inducing autophagy impairment in CSE-treated BEAS-2B cells.

Automated summary

Cigarette smoke (CS)-induced cellular senescence and inadequate autophagy are implicated in the development of chronic obstructive pulmonary disease (COPD). Peroxiredoxin (PRDX) 6, a protein with antioxidant capacity, has been shown to activate autophagy and delay senescence in other diseases. This study investigated the involvement of PRDX6-regulated autophagy in CS extract (CSE)-induced senescence of BEAS-2B cells by silencing PRDX6 expression. Additionally, the GSE20257 dataset revealed lower levels of PRDX6, sirtuin (SIRT) 1, and SIRT6 mRNA, and higher levels of P62 and P16 mRNA in COPD patients compared to non-smokers. Insufficient autophagic clearance of damaged proteins may contribute to accelerated cell senescence in COPD. In conclusion, this study demonstrated a protective role for PRDX6 in COPD and suggested that reduced PRDX6 expression could accelerate senescence by impairing autophagy in CSE-treated BEAS-2B cells.