Zhejiang Provincial Key Laboratory of Interventional Pulmonology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
J Endocrinol. 2023 Aug 17;259(1). doi: 10.1530/JOE-23-0095. Print 2023 Sep 1.
Acute lung injury (ALI) is associated with an increased incidence of respiratory diseases, which are devastating clinical disorders with high global mortality and morbidity. Evidence confirms that fibroblast growth factors (FGFs) play key roles in mediating ALI. Mice were treated with LPS (lipopolysaccharide: 5 mg/kg, intratracheally) to establish an in vivo ALI model. Human lung epithelial BEAS-2B cells cultured in a corresponding medium with LPS were used to mimic the ALI model in vitro. In this study, we characterized FGF10 pretreatment (5 mg/kg, intratracheally) which improved LPS-induced ALI, including histopathological changes, and reduced pulmonary edema. At the cellular level, FGF10 pretreatment (10 ng/mL) alleviated LPS-induced ALI accompanied by reduced reactive oxygen species (ROS) accumulation and inflammatory responses, such as IL-1β, IL-6, and IL-10, as well as suppressed excessive autophagy. Additionally, immunoblotting and co-immunoprecipitation showed that FGF10 activated nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway via Nrf2 nuclear translocation by promoting the interaction between p62 and keap1, thereby preventing LPS-induced ALI. Nrf2 knockout significantly reversed these protective effects of FGF10. Together, FGF10 protects against LPS-induced ALI by restraining autophagy via p62-Kelch-like ECH-associated protein 1 (Keap1)-Nrf2 signaling pathway, implying that FGF10 could be a novel therapy for ALI.
急性肺损伤（ALI）与呼吸疾病的发病率增加有关，而这些疾病是具有高全球死亡率和发病率的破坏性临床疾病。有证据证实成纤维细胞生长因子（FGFs）在介导 ALI 中发挥关键作用。用 LPS（脂多糖：5mg/kg，气管内）处理小鼠以建立体内 ALI 模型。用人肺上皮 BEAS-2B 细胞在相应的 LPS 培养基中培养来模拟体外 ALI 模型。在这项研究中，我们描述了 FGF10 预处理（5mg/kg，气管内）可改善 LPS 诱导的 ALI，包括组织病理学变化和减少肺水肿。在细胞水平上，FGF10 预处理（10ng/mL）减轻了 LPS 诱导的 ALI，同时减少了活性氧（ROS）积累和炎症反应，如 IL-1β、IL-6 和 IL-10，并抑制了过度的自噬。此外，免疫印迹和共免疫沉淀表明，FGF10 通过促进 p62 和 Keap1 之间的相互作用来激活核因子红细胞 2 相关因子 2（Nrf2）信号通路，从而使 Nrf2 核易位，从而防止 LPS 诱导的 ALI。Nrf2 敲除显著逆转了 FGF10 的这些保护作用。总之，FGF10 通过 p62-Kelch 样 ECH 相关蛋白 1（Keap1）-Nrf2 信号通路抑制自噬来保护 LPS 诱导的 ALI，这表明 FGF10 可能成为 ALI 的一种新疗法。
