BPA promotes lung fibrosis in mice by regulating autophagy-dependent ferroptosis in alveolar epithelial cells

Ni Liang; Wenyi Song; Jing Li

doi:10.1016/j.ecoenv.2024.116412

BPA promotes lung fibrosis in mice by regulating autophagy-dependent ferroptosis in alveolar epithelial cells

Ecotoxicol Environ Saf. 2024 Apr 30:278:116412. doi: 10.1016/j.ecoenv.2024.116412. Online ahead of print.

Authors

Ni Liang¹, Wenyi Song¹, Jing Li²

Affiliations

¹ Yunnan Provincial Key Laboratory of Soil Carbon Sequestration and Pollution Control, Faculty of Environmental Science & Engineering, Kunming University of Science & Technology, Kunming, Yunnan 650500, China.
² Yunnan Provincial Key Laboratory of Soil Carbon Sequestration and Pollution Control, Faculty of Environmental Science & Engineering, Kunming University of Science & Technology, Kunming, Yunnan 650500, China. Electronic address: 20212006@kust.edu.cn.

PMID: 38691879
DOI: 10.1016/j.ecoenv.2024.116412

Abstract

Background: Bisphenol A (BPA) is an industrial chemical that is commonly found in daily consumer products. BPA is reportedly associated with lung diseases. However, the impact of BPA on pulmonary fibrosis (PF) and its possible mechanisms of action both remain unclear.

Methods: A PF mouse model was induced by bleomycin (BLM). Mouse lung fibroblasts (MLG 2908) and mouse alveolar epithelial cells (MLE-12) were treated with BPA to establish a PF cell model. Tissue staining, CCK-8 assays, western blot experiments and relevant indicator kits were used to detect and evaluate the effect of BPA on PF.

Results: BPA dose-dependently promoted oxidative stress and induced ferroptosis, leading to PF. The ferroptosis inhibitor Fer-1 partly attenuated the effect of BPA. In addition, among the two main cell types associated with the progression of PF, MLE-12 cells are more sensitive to BPA than are MLG 2908 cells, and BPA induces ferroptosis in MLE-12 cells. Furthermore, BPA promoted autophagy-mediated ferroptosis by activating the AMPK/mTOR signaling pathway, thereby exacerbating the progression of PF. The autophagy inhibitor CQ1 partly attenuated the effect of BPA.

Conclusion: BPA promotes the progression of PF by promoting autophagy-dependent ferroptosis in alveolar epithelial cells, which provides a new theoretical basis for understanding BPA-induced PF.

Keywords: AMPK/mTOR; Autophagy; BPA; Ferroptosis; Lung fibrosis.