Particulate matter promotes the epithelial to mesenchymal transition in human lung epithelial cells via the ROS pathway

Jun Zhang; Xiaoyan Xu; Ying Liang; Xiaomin Wu; Zhongqing Qian; Liming Zhang; Ting Wang

Particulate matter promotes the epithelial to mesenchymal transition in human lung epithelial cells via the ROS pathway

Am J Transl Res. 2023 Aug 15;15(8):5159-5167. eCollection 2023.

Authors

Jun Zhang^{1

2}, Xiaoyan Xu^{1

2}, Ying Liang¹, Xiaomin Wu¹, Zhongqing Qian³, Liming Zhang², Ting Wang^{1

4}

Affiliations

¹ Department of Medicine, University of Arizona Tucson, AZ, USA.
² Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University Beijing, China.
³ Anhui Provincial Key Laboratory of Immunology in Chronic Diseases, Anhui Provincial Key Laboratory of Infection and Immunology, Department of Laboratory Medicine, Bengbu Medical College Bengbu, Anhui, China.
⁴ Center of Translational Science, Florida International University 11350 SW Village Parkway, Port St. Lucie, FL, USA.

PMID: 37692935
PMCID: PMC10492054

Abstract

Objects: Epidemiologic studies have linked exposure to airborne pollutant particulate matter (PM) with increased rates of chronic cardiopulmonary diseases, including asthma and idiopathic pulmonary fibrosis (IPF). Several investigations have suggested that the epithelial-to-mesenchymal transition (EMT) may contribute to the complex pathobiology of environmental exposure-mediated pulmonary fibrosis. The present study was designed to characterize the mechanisms of PM-mediated EMT in human lung epithelial cells (HBECs).

Methods and results: PM induced significant dose (0-100 μg/ml) and time (0-72 h)-dependent increases in transforming growth factor β (TGFβ) and fibronectin (FN) protein levels in HBECs lysates. PM-activated TGFβ and FN protein production in HBECs was prevented by the antioxidant N-acetyl-cysteine (NAC, 5 mM). Furthermore, the NF-κB inhibitor BAY11-7082 (5 μM) abolished PM-induced FN production in HBECs. Biomarkers of EMT (ACTA2, SNAIL1 and SNAIL2) in PM-treated HBECs were significantly increased at the mRNA level compared to control cells.

Conclusions: These results demonstrate that PM increases protein levels of TGFβ and FN via reactive oxygen species (ROS)-dependent pathways. In addition, PM exposure induces EMT in human lung epithelial cells, supporting a novel mechanism for PM-induced pulmonary fibrosis.

Keywords: Particulate matter; epithelial-to-mesenchymal transition; lung epithelial cells; reactive oxygen species.