Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, China.
Cardio-Pulmonary Institute (CPI) and Department of Pulmonary and Critical Care Medicine and Infectious Diseases, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, 35392, Giessen, Germany.
Int Immunopharmacol. 2022 Apr;105:108552. doi: 10.1016/j.intimp.2022.108552. Epub 2022 Feb 2.
Exposure of the lungs to particulate matter (PM) leads to the development of respiratory disease and involves mechanisms such as oxydative stress, mitochondrial dysfunction and endoplasmic reticulum (ER) stress. However, there are no effective therapies to treat PM-induced lung diseases. Fibroblast growth factor 10 (FGF10) is a multifunctional growth factor mediating mesenchymal-to-epithelial signaling and displaying a significant therapeutic potential following injury. The present research aims to investigate the regulatory mechanism of FGF10 on ER stress in PM-induced lung injury. PM-induced lung injury leads to peribronchial wall thickening and marked infiltration of inflammatory cells which is associated with increased secretion of inflammatory cytokines. The results show that FGF10 treatment attenuates PM-induced lung injury in vivo and reversed ER stress protein GRP78 and CHOP levels. Moreover, comparison of human bronchial epithelial cells cultured with PM and FGF10 vs PM alone shows sustained cell proliferation and restrained secretion of inflammatory cytokines supporting FGF10's protective role. Significantly, both ERK1/2 and PI3K/AKT inhibitors largely abolished the impact of FGF10 on PM-induced ER stress. Taken together, both in vivo and in vitro experiments showed that FGF10, via the activation of ERK1/2 and PI3K/AKT signaling, protects against PM-induced lung injury through the regulation of ER stress. Therefore, FGF10 represents a potential therapy for PM-induced lung injury.
肺部暴露于颗粒物 (PM) 会导致呼吸道疾病的发生，并涉及氧化应激、线粒体功能障碍和内质网 (ER) 应激等机制。然而，目前尚无有效的治疗方法来治疗 PM 诱导的肺部疾病。成纤维细胞生长因子 10 (FGF10) 是一种多功能生长因子，介导间充质到上皮的信号转导，并在损伤后显示出显著的治疗潜力。本研究旨在探讨 FGF10 对 PM 诱导的肺损伤中 ER 应激的调节机制。PM 诱导的肺损伤导致细支气管壁增厚和炎症细胞的明显浸润，这与炎症细胞因子的分泌增加有关。结果表明，FGF10 治疗可减轻体内 PM 诱导的肺损伤，并逆转 ER 应激蛋白 GRP78 和 CHOP 水平。此外，与单独用 PM 培养的人支气管上皮细胞相比，用 PM 和 FGF10 培养的细胞显示出持续的细胞增殖和炎症细胞因子分泌的抑制，支持 FGF10 的保护作用。值得注意的是，ERK1/2 和 PI3K/AKT 抑制剂均显著消除了 FGF10 对 PM 诱导的 ER 应激的影响。总之，体内和体外实验均表明，FGF10 通过激活 ERK1/2 和 PI3K/AKT 信号通路，通过调节 ER 应激来保护 PM 诱导的肺损伤。因此，FGF10 可能是一种治疗 PM 诱导的肺损伤的潜在方法。
