Cai Junying, Xu Guohai, Lin Yue, Zhou Bin, Luo Zhenzhong, Yu Shuchun, Lu Jun
Department of Anesthesiology, the Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi, China.
Turk J Biol. 2022 Jul 26;46(6):465-474. doi: 10.55730/1300-0152.2632. eCollection 2022.
Acute lung injury (ALI) is an inflammation of the lungs with high incidence rate and mortality. Ferroptosis is a new cell death, which has influence in body organs. Transient receptor potential vanillin-4 (TRPV4) channel is a key mediator of Ca, its activation induces ferroptosis. The purpose of the study is to investigate the function of TRPV4 on ferroptosis in ALI mice induced by lipopolysaccharide (LPS). In vitro, the regulation of TRPV4 on Ca and ferroptosis was detected by CCK-8, fluorescent probe, and western blot in BEAS-2B cells. In vivo, the role of TRPV4 antagonists on ALI mice was analyzed by determination of pulmonary inflammation, pulmonary edema, and ferroptosis. In vitro, ferroptosis was induced in ALI. TRPV4 expression and intracellular Ca concentration were up-regulated in ALI, and TRPV4 antagonist suppressed LPS-induced ferroptosis in BEAS-2B cells, including decreased MDA and ROS levels, increased GPX4 protein level and cell viability. In vivo, ALI mice showed activated ferroptosis compared with the control group, and administration of TRPV4 inhibition had protective effects on ALI mice, including improving lung pathological characteristics, and reducing the degree of pulmonary edema, inflammation, and ferroptosis. The results manifested that ferroptosis mediated lung injury in LPS-induced ALI, and TRPV4 antagonists might moderate LPS-induced damage by suppressing ferroptosis.
急性肺损伤（ALI）是一种肺部炎症，发病率和死亡率都很高。铁死亡是一种新的细胞死亡方式，对身体器官有影响。瞬时受体电位香草酸受体4（TRPV4）通道是钙离子的关键介质，其激活可诱导铁死亡。本研究旨在探讨TRPV4在脂多糖（LPS）诱导的ALI小鼠铁死亡中的作用。在体外，通过CCK-8、荧光探针和蛋白质免疫印迹法检测BEAS-2B细胞中TRPV4对钙离子和铁死亡的调节作用。在体内，通过测定肺部炎症、肺水肿和铁死亡情况，分析TRPV4拮抗剂对ALI小鼠的作用。在体外，ALI诱导铁死亡。ALI中TRPV4表达和细胞内钙离子浓度上调，TRPV4拮抗剂可抑制LPS诱导的BEAS-2B细胞铁死亡，包括降低丙二醛（MDA）和活性氧（ROS）水平、增加谷胱甘肽过氧化物酶4（GPX4）蛋白水平和细胞活力。在体内，与对照组相比，ALI小鼠表现出铁死亡激活，给予TRPV4抑制对ALI小鼠有保护作用，包括改善肺部病理特征，减轻肺水肿、炎症和铁死亡程度。结果表明，铁死亡介导了LPS诱导的ALI中的肺损伤，TRPV4拮抗剂可能通过抑制铁死亡来减轻LPS诱导的损伤。
