Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
Department of Respiratory Medicine, Affiliated Dongyang Hospital of Wenzhou Medical University, Dongyang 322100, China.
Int Immunopharmacol. 2024 Jun 15;134:112165. doi: 10.1016/j.intimp.2024.112165. Epub 2024 May 1.
Particulate matter (PM) is considered the fundamental component of atmospheric pollutants and is associated with the pathogenesis of many respiratory diseases. Fibroblast growth factor 10 (FGF10) mediates mesenchymal-epithelial signaling and has been linked with the repair process of PM-induced lung injury (PMLI). However, the pathogenic mechanism of PMLI and the specific FGF10 protective mechanism against this injury are still undetermined. PM was administered in vivo into murine airways or in vitro to human bronchial epithelial cells (HBECs), and the inflammatory response and ferroptosis-related proteins SLC7A11 and GPX4 were assessed. The present research investigates the FGF10-mediated regulation of ferroptosis in PMLI mice models in vivo and HBECs in vitro. The results showed that FGF10 pretreatment reduced PM-mediated oxidative damage and ferroptosis in vivo and in vitro. Furthermore, FGF10 pretreatment led to reduced oxidative stress, decreased secretion of inflammatory mediators, and activation of the Nrf2-dependent antioxidant signaling. Additionally, silencing of Nrf2 using siRNA in the context of FGF10 treatment attenuated the effect on ferroptosis. Altogether, both in vivo and in vitro assessments confirmed that FGF10 protects against PMLI by inhibiting ferroptosis via the Nrf2 signaling. Thus, FGF10 can be used as a novel ferroptosis suppressor and a potential treatment target in PMLI.
颗粒物（PM）被认为是大气污染物的基本组成部分，与许多呼吸道疾病的发病机制有关。成纤维细胞生长因子 10（FGF10）介导间质上皮信号转导，与 PM 诱导的肺损伤（PMLI）的修复过程有关。然而，PMLI 的发病机制以及 FGF10 针对这种损伤的具体保护机制仍未确定。本研究将 PM 体内给药到小鼠气道或体外给药到人支气管上皮细胞（HBEC），并评估了炎症反应和铁死亡相关蛋白 SLC7A11 和 GPX4。本研究在体内 PMLI 小鼠模型和体外 HBEC 中研究了 FGF10 介导的铁死亡调节。结果表明，FGF10 预处理可减轻 PM 介导的体内和体外氧化损伤和铁死亡。此外，FGF10 预处理可减少氧化应激，降低炎症介质的分泌，并激活 Nrf2 依赖性抗氧化信号。此外，在 FGF10 处理的情况下使用 siRNA 沉默 Nrf2 会减弱对铁死亡的影响。总之，体内和体外评估均证实，FGF10 通过抑制 Nrf2 信号通路来抑制铁死亡，从而保护 PMLI。因此，FGF10 可作为一种新型的铁死亡抑制剂，并成为 PMLI 的潜在治疗靶点。
