# Atmospheric particulate matter impairs pulmonary barriers by triggering FTH1-mediated ferroptosis

## TL;DR

PM2.5 harms lung function by causing oxidative stress and damaging lung barriers through a process called ferroptosis.

## Contribution

This study identifies FTH1-mediated ferroptosis as a novel mechanism by which PM2.5 induces lung injury.

## Key findings

- PM2.5 exposure compromises lung function and disrupts tissue structure.
- Ferroptosis inhibition with Fer-1 reverses PM2.5-induced damage in lung cells.
- FTH1 is a central regulator in PM2.5-induced lung injury.

## Abstract

PM2.5 exposure is harmful to health. The related mechanisms by which PM2.5 induced acute lung injury remain to be investigated. Herein, we found PM2.5 compromised lung function, disrupted lung tissue histology, and elevated inflammatory cytokines. Transcriptome sequencing data showed that ferroptosis-mediated oxidative stress plays a critical role in both cellular and murine models. In airway epithelial cells, a dose-dependent decrease in junction proteins was observed following PM2.5 induction, which was subsequently ameliorated by the ferroptosis inhibitor Fer-1 treatment. In alveolar macrophages, continuous exposure to PM2.5 for 6 h resulted in diminished phagocytic capacity, which was also reversed upon the addition of Fer-1. Moreover, network analysis identified FTH1 as a central node in regulating PM2.5-induced lung injury. These findings suggest that enhanced pulmonary uptake and retention of PM2.5 correlate with more severe lung injuries, with the number of barriers encountered by PM2.5 during its transit potentially playing a crucial role. The underlying mechanism is partially through disrupting pulmonary barriers via promoting FTH1-mediated ferroptosis.

•PM2.5 impairs airway epithelial barriers•Barrier injury induced by PM2.5 is mediated by ferroptosis-related oxidative stress•FTH1 mitigates PM2.5-induced barrier damage in lung cells

PM2.5 impairs airway epithelial barriers

Barrier injury induced by PM2.5 is mediated by ferroptosis-related oxidative stress

FTH1 mitigates PM2.5-induced barrier damage in lung cells

Biological sciences; Toxicology; Environmental toxicology