Role of the SENP1–SIRT1 pathway in hyperoxia-induced alveolar epithelial cell injury

Abstract

Bronchopulmonary dysplasia (BPD) is a common complication in preterm infants, and its main pathogenesis partly involves oxidative stress. A large number of studies have shown that silent information regulator 1 (SIRT1) plays a protective role in oxidative stress. SUMO-specific protease 1 (SENP1) is vital in the nucleoplasmic distribution of SIRT1 under stress. However, whether the SENP1–SIRT1 pathway is involved in the hyperoxic lung injury is unknown. Therefore, this study aimed to explore the role and related mechanisms of the SENP1–SIRT1 pathway in hyperoxic lung injury. Peripheral blood mononuclear cells (PBMCs) from infants with BPD and SENP1-silenced alveolar epithelial cells were used as research models. PBMCs were isolated from the peripheral blood of premature infants. Next, the SENP1-silenced human alveolar epithelial cells were used to verify the role of the SENP1–SIRT1 pathway in vitro. The results indicated that the ROS level and the mRNA and protein expression of SENP1 increased in PBMCs of infants with BPD, but the expression of SIRT1 decreased in the nucleus and increased in the cytoplasm, and then the expression of acetyl-p53 (Ac-p53) increased. In the hyperoxic alveolar epithelial cell injury model, it seemed that hyperoxia could induce the same variation trend in the SENP1–SIRT1 pathway as in infants with BPD and then increased the expression of Ac-p53 and BAX, and cell apoptosis. Furthermore, silencing SENP1 could alleviate these hyperoxia-induced changes. These results suggested that SENP1 played an important role in hyperoxia-induced lung injury. It could regulate the expression and nucleoplasmic distribution of SIRT1 to inhibit its deacetylase activity, and then promoted cell apoptosis. Hence, SENP1 may become a potential intervention target of BPD in the future.