Zhejiang Provincial Key Laboratory of Interventional Pulmonology, 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, Jinhua 322100, China.
Int Immunopharmacol. 2022 Dec;113(Pt A):109398. doi: 10.1016/j.intimp.2022.109398. Epub 2022 Nov 4.
Particulate matter (PM) is a major environmental contaminant that causes and worsens respiratory diseases. Fibroblast growth factor 10 (FGF10), a paracrine fibroblast growth factor that specifically stimulates repair and regeneration after injury, has been shown to protect against PM-induced lung injury. However, the underlying mechanisms are still unclear. In this study, the protective effects of FGF10 were investigated using a PM-induced lung injury mouse model in vivo and BEAS-2B cells in vitro. According to the findings, FGF10 treatment alleviated PM-induced oxidative damage and pyroptosis in vivo and in vitro. Mechanistically, FGF10 activated antioxidative Nrf2 signaling. Inhibition of PI3K signaling with LY294002 or Nrf2 signaling with ML385 revealed that FGF10-mediated lung protection was mediated by the PI3K/Akt/Nrf2 pathway. These results collectively indicate that FGF10 inhibits oxidative stress-mediated pyroptosis via the PI3K/Akt/Nrf2 pathway, suggesting a possible therapy for PM-induced lung injury.
颗粒物(PM)是一种主要的环境污染物,可导致并加重呼吸道疾病。成纤维细胞生长因子 10(FGF10)是一种旁分泌成纤维细胞生长因子,专门刺激损伤后的修复和再生,已被证明可预防 PM 诱导的肺损伤。然而,其潜在机制尚不清楚。在这项研究中,使用 PM 诱导的肺损伤小鼠模型体内和 BEAS-2B 细胞体外研究了 FGF10 的保护作用。根据研究结果,FGF10 治疗减轻了 PM 诱导的体内和体外氧化损伤和细胞焦亡。从机制上讲,FGF10 激活了抗氧化 Nrf2 信号。用 LY294002 抑制 PI3K 信号或用 ML385 抑制 Nrf2 信号表明,FGF10 介导的肺保护是通过 PI3K/Akt/Nrf2 通路介导的。这些结果共同表明,FGF10 通过 PI3K/Akt/Nrf2 通路抑制氧化应激介导的细胞焦亡,为 PM 诱导的肺损伤提供了一种可能的治疗方法。