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.
Li Liu  1 ,  Qiangqiang Shi  2 ,  Kankai Wang  3 ,  Yao Qian  1 ,  Liqin Zhou  1 ,  Saverio Bellusci  4 ,  Chengshui Chen  5 ,  Nian Dong  6
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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
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.
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