2. Academic Validation
  3. Silica nanoparticles induce lung inflammation in mice via ROS/PARP/TRPM2 signaling-mediated lysosome impairment and autophagy dysfunction

Silica nanoparticles induce lung inflammation in mice via ROS/PARP/TRPM2 signaling-mediated lysosome impairment and autophagy dysfunction

  • Part Fibre Toxicol. 2020 Jun 8;17(1):23. doi: 10.1186/s12989-020-00353-3.
Mingxiang Wang 1,  Jin Li 1,  Shunni Dong 2,  Xiaobo Cai 1 3,  Aili Simaiti 1,  Xin Yang 1,  Xinqiang Zhu 1 4,  Jianhong Luo 5,  Lin-Hua Jiang 6 7,  Binyang Du 8,  Peilin Yu 9,  Wei Yang 10
Affiliations

Affiliations

  • 1 Department of Toxicology, and Department of Medical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China.
  • 2 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science & Engineering, Zhejiang University, Hangzhou, China.
  • 3 Department of Biophysics, and Department of Neurosurgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China.
  • 4 The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, P. R. China.
  • 5 Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, P. R. China.
  • 6 Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University, Xinxiang, P. R. China.
  • 7 School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, LS2 9JT, UK.
  • 8 MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science & Engineering, Zhejiang University, Hangzhou, China. duby@zju.edu.cn.
  • 9 Department of Toxicology, and Department of Medical Oncology of Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China. yupeilin@zju.edu.cn.
  • 10 Department of Biophysics, and Department of Neurosurgery of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China. yangwei@zju.edu.cn.
PMID: 32513195 DOI: 10.1186/s12989-020-00353-3
Abstract

Background: Wide applications of nanoparticles (NPs) have raised increasing concerns about safety to humans. Oxidative stress and inflammation are extensively investigated as mechanisms for NPs-induced toxicity. Autophagy and lysosomal dysfunction are emerging molecular mechanisms. Inhalation is one of the main pathways of exposing humans to NPs, which has been reported to induce severe pulmonary inflammation. However, the underlying mechanisms and, more specifically, the interplays of above-mentioned mechanisms in NPs-induced pulmonary inflammation are still largely obscure. Considered that NPs exposure in modern society is often unavoidable, it is highly desirable to develop effective strategies that could help to prevent nanomaterials-induced pulmonary inflammation.

Results: Pulmonary inflammation induced by intratracheal instillation of silica nanoparticles (SiNPs) in C57BL/6 mice was prevented by PJ34, a poly (ADP-ribose) polymerase (PARP) inhibitor. In human lung bronchial epithelial (BEAS-2B) cells, exposure to SiNPs reduced cell viability, and induced ROS generation, impairment in lysosome function and autophagic flux. Inhibition of ROS generation, PARP and TRPM2 channel suppressed SiNPs-induced lysosome impairment and Autophagy dysfunction and consequent inflammatory responses. Consistently, SiNPs-induced pulmonary inflammation was prevented in TRPM2 deficient mice.

Conclusion: The ROS/PARP/TRPM2 signaling is critical in SiNPs-induced pulmonary inflammation, providing novel mechanistic insights into NPs-induced lung injury. Our study identifies TRPM2 channel as a new target for the development of preventive and therapeutic strategies to mitigate nanomaterials-induced lung inflammation.

Keywords

Autophagy dysfunction; Lysosomal impairment; Nanoparticles; Pulmonary inflammation; ROS/PARP/TRPM2 signaling.

Figures
Products
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  • HY-13688A
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