Fibroblast growth factor 10 protects against particulate matter-induced lung injury by inhibiting oxidative stress-mediated pyroptosis via the PI3K/Akt/Nrf2 signaling pathway

Li Liu; Qiangqiang Shi; Kankai Wang; Yao Qian; Liqin Zhou; Saverio Bellusci; Chengshui Chen; Nian Dong

doi:10.1016/j.intimp.2022.109398

Fibroblast growth factor 10 protects against particulate matter-induced lung injury by inhibiting oxidative stress-mediated pyroptosis via the PI3K/Akt/Nrf2 signaling pathway

Int Immunopharmacol. 2022 Dec;113(Pt A):109398. doi: 10.1016/j.intimp.2022.109398. Epub 2022 Nov 4.

Authors

Li Liu¹, Qiangqiang Shi², Kankai Wang³, Yao Qian¹, Liqin Zhou¹, Saverio Bellusci⁴, Chengshui Chen⁵, Nian Dong⁶

Affiliations

¹ 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.
² Department of Respiratory Medicine, Affiliated Dongyang Hospital of Wenzhou Medical University, Jinhua 322100, China.
³ Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
⁴ Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Cardio-Pulmonary Institute (CPI), Member of the German Center for Lung Research (DZL), Justus-Liebig University Giessen, 35392 Giessen, Germany. Electronic address: Saverio.bellusci@innere.med.uni-giessen.de.
⁵ 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 Pulmonary and Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China. Electronic address: chenchengshui@wmu.edu.cn.
⁶ 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. Electronic address: dongnian@wmu.edu.cn.

PMID: 36461597
DOI: 10.1016/j.intimp.2022.109398

Abstract

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.

Keywords: Fibroblast growth factor 10; Lung injury; Oxidative stress; Particulate matter; Pyroptosis.

MeSH terms

Animals
Fibroblast Growth Factor 10* / genetics
Fibroblast Growth Factor 10* / immunology
Lung Injury* / etiology
Lung Injury* / genetics
Lung Injury* / immunology
Mice
NF-E2-Related Factor 2
Oxidative Stress / genetics
Oxidative Stress / immunology
Particulate Matter* / toxicity
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Pyroptosis* / genetics
Pyroptosis* / immunology
Signal Transduction

Substances

Fibroblast Growth Factor 10
NF-E2-Related Factor 2
Particulate Matter
Phosphatidylinositol 3-Kinases
Proto-Oncogene Proteins c-akt
Fgf10 protein, mouse
Pik3r1 protein, mouse
Akt1 protein, mouse
Nfe2l2 protein, mouse