Sestrin2/Keap1/Nrf2 pathway regulates mucus hypersecretion in pulmonary epithelium induced by traffic-related PM2.5 and water-soluble extracts

Jiayu Tian; Xin Wang; Hao Shi; Hongyan Wu; Caihong Wang; Nannan Liu; Linlin Guan; Zhihong Zhang

doi:10.1016/j.ecoenv.2023.115455

Sestrin2/Keap1/Nrf2 pathway regulates mucus hypersecretion in pulmonary epithelium induced by traffic-related PM_2.5 and water-soluble extracts

Ecotoxicol Environ Saf. 2023 Oct 1:264:115455. doi: 10.1016/j.ecoenv.2023.115455. Epub 2023 Sep 12.

Authors

Jiayu Tian¹, Xin Wang², Hao Shi¹, Hongyan Wu³, Caihong Wang¹, Nannan Liu¹, Linlin Guan¹, Zhihong Zhang⁴

Affiliations

¹ Department of Environmental Health, School of Public Health, Shanxi Medical University, 56 Xinjian South Road, 030001 Taiyuan, Shanxi, China; Center for Ecological Public Health Security of Yellow River Basin, Shanxi Medical University, 56 Xinjian South Road, 030001 Taiyuan, Shanxi, China; Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, China.
² Department of Environmental Health, School of Public Health, Shanxi Medical University, 56 Xinjian South Road, 030001 Taiyuan, Shanxi, China; Yantai Center for Disease Control and Prevention, 264003 Yantai, Shandong, China; Center for Ecological Public Health Security of Yellow River Basin, Shanxi Medical University, 56 Xinjian South Road, 030001 Taiyuan, Shanxi, China; Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, China.
³ Department of Environmental Health, School of Public Health, Shanxi Medical University, 56 Xinjian South Road, 030001 Taiyuan, Shanxi, China; Center for Ecological Public Health Security of Yellow River Basin, Shanxi Medical University, 56 Xinjian South Road, 030001 Taiyuan, Shanxi, China.
⁴ Department of Environmental Health, School of Public Health, Shanxi Medical University, 56 Xinjian South Road, 030001 Taiyuan, Shanxi, China; Center for Ecological Public Health Security of Yellow River Basin, Shanxi Medical University, 56 Xinjian South Road, 030001 Taiyuan, Shanxi, China; Key Laboratory of Coal Environmental Pathogenicity and Prevention (Shanxi Medical University), Ministry of Education, China. Electronic address: zzh1973@sxmu.edu.cn.

PMID: 37708689
DOI: 10.1016/j.ecoenv.2023.115455

Abstract

The involvement of fine particulate matter (PM_2.5) exposure in the progression of asthma has been extensively discussed in epidemiological and experimental evidence, which aroused widespread attention. Asthma is characterized by mucus hypersecretion. This study investigates the underlying toxic mechanism of traffic-related PM_2.5 (TRPM_2.5) and water-soluble extracts (WSE) on mucus hypersecretion in the lungs of rats with asthma and 16HBE cells. The ovalbumin-induced rats were administrated by instillation of TRPM_2.5 and WSE in the trachea once three days for eight times. The results showed that TRPM_2.5 and WSE had an adverse impact on mucus secretion. Specifically, conspicuous mucus stains and increased goblet cells in the bronchial epithelium by PAS staining were found in lung tissues of rats with asthma; MUC5AC gene and protein expression levels in lung tissues of rats with asthma and 16HBE cells were elevated. In addition, TRPM_2.5 and WSE triggered oxidative damage via upregulation of malondialdehyde and myeloperoxidase as well as activation of the Sestrin2/Keap1/Nrf2 signaling pathway. Conversely, the knockdown of Sestrin2 effectively inhibited TRPM_2.5 and WSE-induced mucus hypersecretion, oxidative stress, and Keap1/Nrf2 signaling pathway and its downstream target gene NQO1. Collectively, it was demonstrated that TRPM_2.5 and WSE induced mucus hypersecretion mediated by the Sestrin2/Keap1/Nrf2 pathway.

Keywords: Asthma; Mucus hypersecretion; Sestrin2/Keap1/Nrf2; Traffic-related PM(2.5); Water-soluble extracts.

MeSH terms

Animals
Asthma* / chemically induced
Coloring Agents
Epithelium
Kelch-Like ECH-Associated Protein 1 / genetics
Lung
Mucus
NF-E2-Related Factor 2 / genetics
Rats
TRPM Cation Channels*

Substances

NF-E2-Related Factor 2
Kelch-Like ECH-Associated Protein 1
TRPM Cation Channels
Coloring Agents