PMID- 33162208 OWN - NLM STAT- MEDLINE DCOM- 20201218 LR - 20201218 IS - 1873-6424 (Electronic) IS - 0269-7491 (Linking) VI - 268 IP - Pt A DP - 2021 Jan 1 TI - LncRNA H19-mediated M2 polarization of macrophages promotes myofibroblast differentiation in pulmonary fibrosis induced by arsenic exposure. PG - 115810 LID - S0269-7491(20)36499-X [pii] LID - 10.1016/j.envpol.2020.115810 [doi] AB - Arsenic is a potent toxicant, and long-term exposure to inorganic arsenic causes lung damage. M2 macrophages play an important role in the pathogenesis of pulmonary fibrosis. However, the potential connections between arsenic and M2 macrophages in the development of pulmonary fibrosis are elusive. C57BL/6 mice were fed with drinking water containing 0, 10 and 20 ppm arsenite for 12 months. We have found that, in lung tissues of mice, arsenite, a biologically active form of arsenic, elevated H19, c-Myc, and Arg1; decreased let-7a; and caused pulmonary fibrosis. For THP-1 macrophages (THP-M) and bone-marrow-derived macrophages (BMDMs), 8 muM arsenite increased H19, c-Myc, and Arg1; decreased let-7a; and induced M2 polarization of macrophages, which caused secretion of the fibrogenic cytokine, TGF-beta1. Down-regulation of H19 or up-regulation of let-7a reversed the arsenite-induced M2 polarization of macrophages. Arsenite-treated THP-M and BMDMs co-cultured with MRC-5 cells or primary lung fibroblasts (PLFs) elevated levels of p-SMAD2/3, SMAD4, alpha-SMA, and collagen I in lung fibroblasts and resulted in the activation of lung fibroblasts. Knockout of H19 or up-regulation of let-7a in macrophages reversed the effects. The results indicated that H19 functioned as an miRNA sponge for let-7a, which was involved in arsenite-induced M2 polarization of macrophages and induced the myofibroblast differentiation phenotype by regulation of c-Myc. In the sera of arseniasis patients, levels of hydroxyproline and H19 were higher, and levels of let-7a were lower than levels in the controls. These observations elucidate a possible mechanism for arsenic exposure-induced pulmonary fibrosis. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Xiao, Tian AU - Xiao T AD - Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China. FAU - Zou, Zhonglan AU - Zou Z AD - The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 550025, Guizhou, People's Republic of China. FAU - Xue, Junchao AU - Xue J AD - Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China. FAU - Syed, Binafsha Manzoor AU - Syed BM AD - Medical Research Centre, Liaquat University of Medical & Health Sciences, Jamshoro, 76090, Sindh, Pakistan. FAU - Sun, Jing AU - Sun J AD - Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China. FAU - Dai, Xiangyu AU - Dai X AD - Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China. FAU - Shi, Ming AU - Shi M AD - Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong, People's Republic of China. FAU - Li, Junjie AU - Li J AD - Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China. FAU - Wei, Shaofeng AU - Wei S AD - The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 550025, Guizhou, People's Republic of China. FAU - Tang, Huanwen AU - Tang H AD - Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan, 523808, Guangdong, People's Republic of China. FAU - Zhang, Aihua AU - Zhang A AD - The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, School of Public Health, Guizhou Medical University, Guiyang, 550025, Guizhou, People's Republic of China. FAU - Liu, Qizhan AU - Liu Q AD - Center for Global Health, The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, People's Republic of China. Electronic address: drqzliu@hotmail.com. LA - eng PT - Journal Article DEP - 20201027 PL - England TA - Environ Pollut JT - Environmental pollution (Barking, Essex : 1987) JID - 8804476 RN - 0 (MicroRNAs) RN - 0 (RNA, Long Noncoding) RN - N712M78A8G (Arsenic) SB - IM MH - Animals MH - *Arsenic/toxicity MH - Cell Differentiation MH - Humans MH - Macrophages MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - *MicroRNAs/genetics MH - Myofibroblasts MH - *Pulmonary Fibrosis/chemically induced MH - *RNA, Long Noncoding/genetics OTO - NOTNLM OT - Arsenic exposure OT - Macrophages OT - Pulmonary fibrosis OT - lncRNAs OT - microRNAs COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/11/10 06:00 MHDA- 2020/12/19 06:00 CRDT- 2020/11/09 05:27 PHST- 2020/08/06 00:00 [received] PHST- 2020/10/02 00:00 [revised] PHST- 2020/10/09 00:00 [accepted] PHST- 2020/11/10 06:00 [pubmed] PHST- 2020/12/19 06:00 [medline] PHST- 2020/11/09 05:27 [entrez] AID - S0269-7491(20)36499-X [pii] AID - 10.1016/j.envpol.2020.115810 [doi] PST - ppublish SO - Environ Pollut. 2021 Jan 1;268(Pt A):115810. doi: 10.1016/j.envpol.2020.115810. Epub 2020 Oct 27.