2. Academic Validation
  3. Fine particulate matter exacerbates childhood asthma via DNMT3A-mediated modulation of GPX4 DNA methylation

Fine particulate matter exacerbates childhood asthma via DNMT3A-mediated modulation of GPX4 DNA methylation

  • Sci Rep. 2026 Jan 16;16(1):5566. doi: 10.1038/s41598-026-35962-z.
Xiaolu Wu 1 2,  Liangzhe Dai 3,  Ran Li 4 5,  Xia Chi 6
Affiliations

Affiliations

  • 1 Department of Child Health Care, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China.
  • 2 Department of Pediatrics, The First Affiliated Hospital With Nanjing Medical University, Nanjing, China.
  • 3 The First Clinical Medical College, Nanjing Medical University, Nanjing, China.
  • 4 Department of Child Health Care, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China. [email protected].
  • 5 Department of Hematology, The First Affiliated Hospital With Nanjing Medical University, Nanjing, China. [email protected].
  • 6 Department of Child Health Care, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China. [email protected].
PMID: 41545575 DOI: 10.1038/s41598-026-35962-z
Abstract

Fine particulate matter measuring less than 2.5 μm in diameter (PM(2.5)) is a significant risk factor for acute asthma episodes in children. Nevertheless, the biological mechanism that underpins this correlation remains unclear. Here, we found that PM(2.5)-induced inflammatory cell infiltration and aggravated childhood asthma in a ferroptosis-dependent manner. GPX4 overexpression could reverse the PM(2.5)-induced increase in Reactive Oxygen Species (ROS), malondialdehyde (MDA), and inflammatory factors, as well as the decrease in mitochondrial membrane potential. Mechanistically, PM(2.5) elevated DNMT3A expression and hypermethylated the promoter region of GPX4, leading to reduced GPX4 expression and promoting Ferroptosis. Furthermore, the status of GPX4 DNA methylation was significantly associated with IL-6/8 levels in mild/moderate and severe childhood asthma patients. In conclusion, our research highlights the critical interplay between PM(2.5) exposure, DNA methylation, and Ferroptosis in asthma exacerbation, providing clues for the treatment of childhood asthma.

Keywords

Childhood asthma exacerbation; DNA methylation; Ferroptosis; IL-6/8; PM(2.5).

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