{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T02:01:18Z","timestamp":1760061678388},"reference-count":44,"publisher":"Hindawi Limited","license":[{"start":{"date-parts":[[2015,1,1]],"date-time":"2015-01-01T00:00:00Z","timestamp":1420070400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2015]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Paraquat (PQ) poisoning is a lethal toxicological challenge that served as a disease model of acute lung injury and pulmonary fibrosis, but the mechanism is undetermined and no effective treatment has been discovered.<jats:italic>Methods and Findings<\/jats:italic>. We demonstrated that PQ injures mitochondria and leads to mtDNA release. The mtDNA mediated PBMC recruitment and stimulated the alveolar epithelial cell production of TGF-<jats:italic>\u03b2<\/jats:italic>1 in vitro. The levels of mtDNA in circulation and bronchial alveolar lavage fluid (BALF) were elevated in a mouse of PQ-induced lung injury. DNaseI could protect PQ-induced lung injury and significantly improved survival. Acute lung injury markers, such as TNF<jats:italic>\u03b1<\/jats:italic>, IL-1<jats:italic>\u03b2<\/jats:italic>, and IL-6, and marker of fibrosis, collagen I, were downregulated in parallel with the elimination of mtDNA by DNaseI. These data indicate a possible mechanism for PQ-induced, mtDNA-mediated lung injury, which may be shared by other causes of lung injury, as suggested by the same protective effect of DNaseI in bleomycin-induced lung injury model. Interestingly, increased mtDNA in the BALF of patients with amyopathic dermatomyositis-interstitial lung disease can be appreciated.<jats:italic>Conclusions<\/jats:italic>. DNaseI targeting mtDNA may be a promising approach for the treatment of PQ-induced acute lung injury and pulmonary fibrosis that merits fast tracking through clinical trials.<\/jats:p>","DOI":"10.1155\/2015\/386952","type":"journal-article","created":{"date-parts":[[2015,2,11]],"date-time":"2015-02-11T21:06:17Z","timestamp":1423688777000},"page":"1-10","source":"Crossref","is-referenced-by-count":9,"title":["DNaseI Protects against Paraquat-Induced Acute Lung Injury and Pulmonary Fibrosis Mediated by Mitochondrial DNA"],"prefix":"10.1155","volume":"2015","author":[{"given":"Guo","family":"Li","sequence":"first","affiliation":[{"name":"Department of Rheumatology, South Campus, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Yuzhen","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong 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