Related Experiment Video
Updated: Jan 18, 2026
Identification and Characterization of Immunogenic RNA Species in HDM Allergens that Modulate Eosinophilic Lung Inflammation
Published on: May 30, 2020
Fine particulate matter exacerbates childhood asthma via DNMT3A-mediated modulation of GPX4 DNA methylation
Xiaolu Wu1,2, Liangzhe Dai3, Ran Li4,5
1Department of Child Health Care, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing, China.
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.
Insights
Fine particulate matter (PM2.5) exposure exacerbates childhood asthma by triggering ferroptosis, a cell death pathway. This occurs through PM2.5-induced DNA methylation of GPX4, a key regulator, highlighting a novel therapeutic target.
Area of Science:
- Environmental Health
- Molecular Biology
- Pediatric Pulmonology
Background:
- Fine particulate matter (PM2.5) is a known risk factor for childhood asthma exacerbations.
- The precise biological mechanisms linking PM2.5 exposure to asthma pathogenesis remain largely undefined.
Purpose of the Study:
- To elucidate the molecular mechanisms by which PM2.5 exposure aggravates childhood asthma.
- To investigate the role of ferroptosis and DNA methylation in PM2.5-induced asthma exacerbation.
Main Methods:
- Investigated the impact of PM2.5 exposure on inflammatory cell infiltration and asthma severity in a pediatric model.
- Analyzed the expression of GPX4, reactive oxygen species (ROS), malondialdehyde (MDA), and mitochondrial membrane potential.
- Examined the role of DNMT3A, DNA methylation of the GPX4 promoter, and its association with inflammatory markers (IL-6/8) in asthma patients.
Main Results:
- PM2.5 exposure induced inflammatory cell infiltration and worsened childhood asthma via a ferroptosis-dependent pathway.
- GPX4 overexpression counteracted PM2.5-induced oxidative stress and inflammation.
- PM2.5 exposure increased DNMT3A, leading to GPX4 promoter hypermethylation, reduced GPX4 expression, and ferroptosis.
- GPX4 DNA methylation levels correlated with IL-6/8 levels in childhood asthma patients.
Conclusions:
- PM2.5 exposure, DNA methylation, and ferroptosis are critically interconnected in the exacerbation of childhood asthma.
- Targeting GPX4 methylation offers a potential therapeutic strategy for PM2.5-related pediatric asthma.
Related Concept Videos
01:20Asthma: Pathogenesis and Management
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
01:29Asthma-I: Introduction
01:26Asthma-II: Pathophysiology and Classification
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
01:19Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
01:30Asthma-IV: Diagnostic and Management
Clinical Assessment for Asthma:
This is the first step in diagnosing and managing asthma. It includes:
01:25Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...