ROS-mediated MAPK activation aggravates hyperoxia-induced acute lung injury by promoting apoptosis of type II alveolar epithelial cells via the STAT3/miR-21-5p axis

Abstract

Inhibition of type II alveolar epithelial (AE-II) cell apoptosis is a critical way to cure hyperoxia-induced acute lung injury (HALI). It has been reported that miR-21-5p could reduce H₂O₂-induced apoptosis in AE-II cells. However, the upstream molecular mechanism remains unclear. Herein, we established a cellular model of HALI by exposing AE-II cells to H₂O₂ treatment. It was shown that miR-21-5p alleviated H₂O₂-induced apoptosis in AE-II cells. ROS inhibition decreased apoptosis of H₂O₂-evoked AE-II cells via increasing miR-21-5p expression. In addition, ROS induced MAPK and STAT3 phosphorylation in H₂O₂-treated AE-II cells. MAPK inactivation reduces H₂O₂-triggered AE-II cell apoptosis. MAPK activation inhibits miR-21-5p expression by promoting STAT3 phosphorylation in H₂O₂-challenged AE-II cells. Furthermore, STAT3 activation eliminated MAPK deactivation-mediated inhibition on the apoptosis of AE-II cells under H₂O₂ condition. In conclusion, ROS-mediated MAPK activation promoted H₂O₂-triggered AE-II cell apoptosis by inhibiting miR-21-5p expression via STAT3 phosphorylation, providing novel targets for HALI treatment.

Keywords: Hyperoxia-induced acute lung injury; MAPK; MiR-21–5p; ROS; STAT3.