Liu Ruihan, Wang Zhihui, Luo Qing, Song Guanbin
Key Laboratory of Biorheological Science and Technology, College of Bioengineering, Chongqing University, Chongqing, 400030, China.
Key Laboratory of Biorheological Science and Technology, College of Bioengineering, Chongqing University, Chongqing, 400030, China.
J Therm Biol. 2025 Jan;127:104065. doi: 10.1016/j.jtherbio.2025.104065. Epub 2025 Jan 28.
Inhalation lung injury is an acute pulmonary impairment resulting from inhalation of hot air and/or toxic gases. However, the molecular mechanisms involved in hot air-induced heat stress (HS) response of alveolar epithelial cells are not fully understood. In this study, employing a cell heat loading device, we found that HS at 50 °C resulted in significant ferroptosis and injury of human alveolar epithelial cells (BEAS-2B cells), supported by increased lipid peroxidation, reactive oxygen species (ROS), and decreased ferritin heavy chain 1 (FTH1), glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11). Ferrostatin-1 (Fer-1), a targeted inhibitor of ferroptosis, could suppress HS-induced ferroptosis and injury of BEAS-2B cells. Moreover, HS activated extracellular signal-regulated kinase 1/2 (ERK1/2) in BEAS-2B cells. Nevertheless, blockage of ERK1/2 activation by U0126, an inhibitor of ERK1/2 phosphorylation, repressed HS-induced ferroptosis and injury of BEAS-2B cells. Taken together, this study demonstrates that HS injures alveolar epithelial cells through ERK1/2 signaling-mediated ferroptosis, which provides a novel potential strategy for the treatment of HS-induced inhalation lung injury.
吸入性肺损伤是由于吸入热空气和/或有毒气体导致的急性肺损伤。然而，肺泡上皮细胞热空气诱导的热应激（HS）反应所涉及的分子机制尚未完全阐明。在本研究中，我们使用细胞热加载装置发现，50°C的热应激导致人肺泡上皮细胞（BEAS-2B细胞）发生显著的铁死亡和损伤，脂质过氧化、活性氧（ROS）增加以及铁蛋白重链1（FTH1）、谷胱甘肽过氧化物酶4（GPX4）、溶质载体家族7成员11（SLC7A11）减少均支持这一结果。铁死亡靶向抑制剂铁抑素-1（Fer-1）可抑制热应激诱导的BEAS-2B细胞铁死亡和损伤。此外，热应激激活了BEAS-2B细胞中的细胞外信号调节激酶1/2（ERK1/2）。然而，ERK1/2磷酸化抑制剂U0126阻断ERK1/2激活可抑制热应激诱导的BEAS-2B细胞铁死亡和损伤。综上所述，本研究表明热应激通过ERK1/2信号介导的铁死亡损伤肺泡上皮细胞，这为治疗热应激诱导的吸入性肺损伤提供了一种新的潜在策略。
