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

Ecotoxicology and Environmental Safety (Oct 2023)

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

Affiliations

Jiayu Tian: 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
Xin Wang: 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
Hao Shi: 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
Hongyan Wu: 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
Caihong Wang: 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
Nannan Liu: 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
Linlin Guan: 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
Zhihong Zhang: 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; Corresponding author at: Department of Environmental Health, School of Public Health, Shanxi Medical University, 56 Xinjian South Road, 030001 Taiyuan, Shanxi, China.

Journal volume & issue: Vol. 264
p. 115455

Abstract

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The involvement of fine particulate matter (PM2.5) 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 PM2.5 (TRPM2.5) 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 TRPM2.5 and WSE in the trachea once three days for eight times. The results showed that TRPM2.5 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, TRPM2.5 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 TRPM2.5 and WSE-induced mucus hypersecretion, oxidative stress, and Keap1/Nrf2 signaling pathway and its downstream target gene NQO1. Collectively, it was demonstrated that TRPM2.5 and WSE induced mucus hypersecretion mediated by the Sestrin2/Keap1/Nrf2 pathway.

Published in Ecotoxicology and Environmental Safety

ISSN: 0147-6513 (Print); 1090-2414 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Technology: Environmental technology. Sanitary engineering: Environmental pollution; Geography. Anthropology. Recreation: Environmental sciences
Website: https://www.journals.elsevier.com/ecotoxicology-and-environmental-safety

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