Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, PR China.
Department of Pediatric, The second affiliated Hospital of Zunyi Medical University, Zunyi 563000, PR China.
Mol Immunol. 2023 Nov;163:207-215. doi: 10.1016/j.molimm.2023.09.016. Epub 2023 Oct 14.
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 HO-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 HO treatment. It was shown that miR-21-5p alleviated HO-induced apoptosis in AE-II cells. ROS inhibition decreased apoptosis of HO-evoked AE-II cells via increasing miR-21-5p expression. In addition, ROS induced MAPK and STAT3 phosphorylation in HO-treated AE-II cells. MAPK inactivation reduces HO-triggered AE-II cell apoptosis. MAPK activation inhibits miR-21-5p expression by promoting STAT3 phosphorylation in HO-challenged AE-II cells. Furthermore, STAT3 activation eliminated MAPK deactivation-mediated inhibition on the apoptosis of AE-II cells under HO condition. In conclusion, ROS-mediated MAPK activation promoted HO-triggered AE-II cell apoptosis by inhibiting miR-21-5p expression via STAT3 phosphorylation, providing novel targets for HALI treatment.
抑制 II 型肺泡上皮（AE-II）细胞凋亡是治疗高氧诱导急性肺损伤（HALI）的关键途径。据报道，miR-21-5p 可以减少 HO 诱导的 AE-II 细胞凋亡。然而，上游分子机制尚不清楚。在此，我们通过用 HO 处理 AE-II 细胞建立了 HALI 的细胞模型。结果表明，miR-21-5p 减轻了 HO 诱导的 AE-II 细胞凋亡。ROS 抑制通过增加 miR-21-5p 的表达减少了 HO 诱导的 AE-II 细胞凋亡。此外，ROS 诱导了 HO 处理的 AE-II 细胞中 MAPK 和 STAT3 的磷酸化。MAPK 失活减少了 HO 触发的 AE-II 细胞凋亡。MAPK 激活通过促进 HO 挑战的 AE-II 细胞中 STAT3 的磷酸化来抑制 miR-21-5p 的表达。此外，STAT3 的激活消除了 MAPK 失活介导的在 HO 条件下对 AE-II 细胞凋亡的抑制。总之，ROS 介导的 MAPK 激活通过抑制 miR-21-5p 的表达促进了 HO 触发的 AE-II 细胞凋亡，为 HALI 的治疗提供了新的靶点。
