DNaseI protects against Paraquat-induced acute lung injury and pulmonary fibrosis mediated by mitochondrial DNA

BioMed Research International
Guo LiYe Shuang

Abstract

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. 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-β1 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 TNFα, IL-1β, 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. DNaseI targeting mtDNA may be a promising approach for the treatment of PQ-induced acute lung injury and ...Continue Reading

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Citations

Oct 1, 2015·Biomedical Chromatography : BMC·Congcong WenXianqin Wang
Nov 6, 2018·PloS One·Marcia Rodrigues da SilvaAdriana Lino-Dos-Santos-Franco
Nov 8, 2018·Singapore Medical Journal·Nan FengJie Chen
Mar 2, 2016·The Journal of Clinical Investigation·Suzanne M Cloonan, Augustine M K Choi
Jul 28, 2019·Journal of Biochemical and Molecular Toxicology·Sayed Mahdi MarashiForouzan Khodaei
Jul 30, 2020·Oxidative Medicine and Cellular Longevity·Hao SunJian Kang
Aug 31, 2021·Toxicology Mechanisms and Methods·Na WangMin Zhao

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Methods Mentioned

BETA
ELISA
PCR
Flow Cytometry

Software Mentioned

GraphPad Prism

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