2. Academic Validation
  3. Parkin deficiency exacerbates particulate matter-induced injury by enhancing airway epithelial necroptosis

Parkin deficiency exacerbates particulate matter-induced injury by enhancing airway epithelial necroptosis

  • Sci Total Environ. 2024 Nov 25:953:175922. doi: 10.1016/j.scitotenv.2024.175922.
Yuting Lin 1,  Meiyu Quan 2,  Xibin Wang 2,  Wanqi Miao 2,  Haibo Xu 2,  Baiqi He 2,  Bin Liu 2,  Yanxia Zhang 3,  Yijing Chen 2,  Binqian Zhou 2,  Mengying Xu 2,  Li Dong 2,  Xuru Jin 4,  Zhenkun Lou 5,  Jin-San Zhang 6,  Chengshui Chen 7
Affiliations

Affiliations

  • 1 Department of Pulmonary and Critical Care Medicine, Key Laboratory of Interventional Pulmonology of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Department of Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
  • 2 Department of Pulmonary and Critical Care Medicine, Key Laboratory of Interventional Pulmonology of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
  • 3 Department of Pulmonary and Critical Care Medicine, Key Laboratory of Interventional Pulmonology of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Medical Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China.
  • 4 Department of Pulmonary and Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China.
  • 5 Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN 55905, USA; Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA.
  • 6 Department of Pulmonary and Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou 324000, China; Medical Research Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, China; Department of Oncology, Mayo Clinic, Rochester, MN 55905, USA. Electronic address: Zhang_jinsan@wmu.edu.cn.
  • 7 Department of Pulmonary and Critical Care Medicine, Key Laboratory of Interventional Pulmonology of Zhejiang Province, 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.
PMID: 39218088 DOI: 10.1016/j.scitotenv.2024.175922
Abstract

Exposure to fine particulate matter (PM) disrupts the function of airway epithelial barriers causing cellular stress and damage. However, the precise mechanisms underlying PM-induced cellular injury and the associated molecular pathways remain incompletely understood. In this study, we used intratracheal instillation of PM in C57BL6 mice and PM treatment of the BEAS-2B cell line as in vivo and in vitro models, respectively, to simulate PM-induced cellular damage and inflammation. We collected lung tissues and bronchoalveolar lavage fluids to assess histopathological changes, Necroptosis, and airway inflammation. Our findings reveal that PM exposure induces Necroptosis in mouse airway epithelial cells. Importantly, concurrent administration of a receptor interacting protein kinases 3 (RIPK3) inhibitor or the deletion of the Necroptosis effector mixed-lineage kinase domain-like protein (MLKL) effectively attenuated PM-induced airway inflammation. PM exposure dose-dependently induces the expression of Parkin, an E3 Ligase we recently reported to play a pivotal role in Necroptosis through regulating necrosome formation. Significantly, deletion of endogenous Parkin exacerbates inflammation by enhancing epithelial Necroptosis. These results indicate that PM-induced Parkin expression plays a crucial role in suppressing epithelial Necroptosis, thereby reducing airway inflammation. Overall, these findings offer valuable mechanistic insights into PM-induced airway injury and identify a potential target for clinical intervention.

Keywords

Airway injury; Inflammation; Necroptosis; Parkin; Particulate matter (PM); Transgenic mice.

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