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In this study, we generated a silicosis model by intratracheal instillation of silica, and then performed histopathological, biochemical, and transcriptomic analysis to evaluate the role of NMN in silicosis. We found that NMN mitigated lung damage at 7 and 28 days, manifested as a decreasing coefficient of lung weight and histological changes, and alleviated oxidative damage by reducing levels of reactive oxygen species and increasing glutathione. Meanwhile, NMN treatment also reduced the recruitment of inflammatory cells and inflammatory infiltration in lung tissue. Transcriptomic analysis showed that NMN treatment mainly regulated immune response and glutathione metabolism pathways. Additionally, NMN upregulated the expression of antioxidant genes Gstm1, Gstm2, and Mgst1 by promoting the expression and nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf2). Gene interaction analysis showed that Nrf2 interacted with Gstm1 and Mgst1 through Gtsm2. Promisingly, oxidative damage mediated by these genes occurred mainly in fibroblasts. In summary, NMN alleviates silica-induced oxidative stress and lung injury by regulating the endogenous glutathione metabolism pathways. This study reveals that NMN supplementation might be a promising strategy for mitigating oxidative stress and inflammation in silicosis.<\/jats:p>","DOI":"10.3390\/nu15010143","type":"journal-article","created":{"date-parts":[[2022,12,28]],"date-time":"2022-12-28T05:30:27Z","timestamp":1672205427000},"page":"143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Nicotinamide Mononucleotide Ameliorates Silica-Induced Lung Injury through the Nrf2-Regulated Glutathione Metabolism Pathway in Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Liqun","family":"Wang","sequence":"first","affiliation":[{"name":"Molecular Toxicology Laboratory of Sichuan Provincial Education Office, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China"},{"name":"West China Occupational Pneumoconiosis Cohort Study (WCOPCS) Working Group, Research Center for Prevention and Therapy of Occupational Disease, West China-PUMC C.C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Laboratory of Sichuan Provincial Education Office, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China"},{"name":"West China Occupational Pneumoconiosis Cohort Study (WCOPCS) Working Group, Research Center for Prevention and Therapy of Occupational Disease, West China-PUMC C.C. Chen Institute of Health, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Qian","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Laboratory of Sichuan Provincial Education Office, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengzhu","family":"Wang","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Laboratory of Sichuan Provincial Education Office, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixue","family":"Bao","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Laboratory of Sichuan Provincial Education Office, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuxi","family":"Chen","sequence":"additional","affiliation":[{"name":"Molecular Toxicology Laboratory of Sichuan Provincial Education Office, Institute of Systems Epidemiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu 610041, China"},{"name":"West China Occupational Pneumoconiosis Cohort Study (WCOPCS) Working Group, Research Center for Prevention and Therapy of Occupational Disease, West China-PUMC C.C. 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