FGF10 protects against particulate matter (PM)-induced lung injury via regulation of endoplasmic reticulum stress.

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. Copyright © 2022 Elsevier B.V. All rights reserved.

Citation

Qiangqiang Shi, Qiang Wang, Li Liu, Junjie Chen, Beibei Wang, Saverio Bellusci, Chengshui Chen, Nian Dong. FGF10 protects against particulate matter (PM)-induced lung injury via regulation of endoplasmic reticulum stress. International immunopharmacology. 2022 Apr;105:108552

Mesh Tags

Substances

PMID: 35114441

search → result