2. Academic Validation
  3. SiO2 NP promotes allergic gastritis induced by degranulation of mouse MC9 cell through AQP4-mediated impairment of SIRT3-TFAM deacetylation and mitochondrial autophagy

SiO2 NP promotes allergic gastritis induced by degranulation of mouse MC9 cell through AQP4-mediated impairment of SIRT3-TFAM deacetylation and mitochondrial autophagy

  • J Hazard Mater. 2025 Oct 5:497:139721. doi: 10.1016/j.jhazmat.2025.139721.
Yutian Lei 1,  Xiaodan Wang 1,  Hao Wu 1,  Meichen Gao 1,  Tong Xu 2,  Hongjin Lin 3
Affiliations

Affiliations

  • 1 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.
  • 2 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Laboratory of Embryo Biotechnology, College of Life Science, Northeast Agricultural University, Harbin 150030, PR China. Electronic address: tongxu@neau.edu.cn.
  • 3 College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Laboratory of Embryo Biotechnology, College of Life Science, Northeast Agricultural University, Harbin 150030, PR China. Electronic address: linhongjin@neau.edu.cn.
PMID: 40916298 DOI: 10.1016/j.jhazmat.2025.139721
Abstract

Silicon dioxide nanoparticles (SiO2 NPs) are a novel material with a wide range of applications whose cumulative effects in the body pose certain health risks. The types of gastric injuries caused by different-sized SiO2 NPs and their mechanisms, however, remain unclear. Based on this, we established a mouse subchronic exposure model (10 mg/kg/d, 21 consecutive days of tube-feeding) with different SiO2 NP sizes (50, 300, and 1000 nm) in conjunction with in vitro MC9 and BMMCs models (160 μg/mL exposure for 24 h) to explore the gastric injury mechanisms. The results showed that SiO2 NP exposure mediated oxidative stress after activating AQP4 water channels, and interfered with the deacetylation of TFAM by SIRT3 while enhancing the ability of TMEM175 to efflux protons. This resulted in mitochondrial dysfunction and lysosomal damage, a decrease in autophagic flux, a massive release of mtDNA into the cytoplasm, and the downstream activation of NLRP3 inflammasomes that induced Pyroptosis. This leads to degranulation of the mast cells and release of inflammatory factors. Moreover, SiO2 NP with a particle size of 300 nm were the most toxic. CONCLUSION: SiO2 NP promote allergic gastritis induced by the degranulation of mouse mast cells through the AQP4-mediated impairment of SIRT3-TFAM deacetylation and mitochondrial Autophagy. This study reveals a new mechanism of nanoparticle immunotoxicity through AQP4-mediated epigenetic modification (SIRT3-TFAM deacetylation), and establishes a particle size-effect model with 300 nm as the critical value of nanoparticle gastric toxicity. These findings provide specific biomarkers (e.g., TFAM acetylation levels) for the early detection of gastrointestinal side effects of nanomedicines, where modulation of SIRT3 activity or targeting of the TMEM175 channel may be potential strategies for combating nanomaterial-induced allergic reactions.

Keywords

Allergic gastritis; Lysosomal dysfunction; Mast cells degranulation; Mitochondrial autophagy; SIRT3-TFAM deacetylation; SiO(2) NP.

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