期刊
ENVIRONMENTAL POLLUTION
卷 283, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.envpol.2021.117134
关键词
1-Nitropyrene; Epithelial-mesenchymal transition; Endoplasmic reticulum stress; Reactive oxygen species; Pulmonary fibrosis
资金
- National Natural Science Foundation of China [81670060, 91743105]
- National Natural Science Foundation Incubation Program of the Second Affiliated Hospital of Anhui Medical University [2020GQFY05]
Chronic exposure to 1-nitropyrene (1-NP) induces pulmonary fibrosis in mice, potentially through oxidative stress-induced endoplasmic reticulum stress leading to epithelial-mesenchymal transition.
1-Nitropyrene (1-NP) is one component of atmospheric fine particles. Previous report revealed that acute 1-NP exposure induced respiratory inflammation. This study aimed to investigate whether chronic 1-NP exposure induces pulmonary fibrosis. Male C57BL6/J mice were intratracheally instilled to 1-NP (20 mu g/mouse/week) for 6 weeks. Diffuse interstitial inflammation, a-smooth muscle actin (a-SMA)-positive cells, a marker of epithelial-mesenchymal transition (EMT), and an extensive collagen deposition, measured by Masson staining, were observed in 1-NP-exposed mouse lungs. Pulmonary function showed that lung dynamic compliance (Cydn-min) was reduced in 1-NP-exposed mice. Conversely, inspiratory resistance (Ri) and expiratory resistance (Re) were elevated in 1-NP-exposed mice. Mechanistically, cell migration and invasion were accelerated in 1-NP-exposed pulmonary epithelial cells. In addition, E-cadherin, an epithelial marker, was downregulated, and vimentin, a-SMA and N-cadherin, three mesenchymal markers, were upregulated in 1-NP-exposed pulmonary epithelial cells. Although TGF-beta wasn't altered, phosphorylated Smad2/3 were enhanced in 1-NP-exposed pulmonary epithelial cells. Moreover, reactive oxygen species (ROS) were increased and endoplasmic reticulum (ER) stress was activated in 1-NP-exposed pulmonary epithelial cells. N-Acetylcysteine (NAC), an antioxidant, attenuated 1-NP-evoked excess ROS, ER stress and EMT in pulmonary epithelial cells. Similarly, pretreatment with NAC alleviated 1-NP-caused pulmonary EMT and lung fibrosis in mice. These results demonstrate that ROS-evoked ER stress contributes, at least partially, to 1-NP-induced EMT and pulmonary fibrosis. (C) 2021 Elsevier Ltd. All rights reserved.
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