title: miR-489 inhibits silica-induced pulmonary fibrosis by targeting MyD88 and Smad3 and is negatively regulated by lncRNA CHRF.
abstract: Silicosis is an incurable occupational disease associated with inflammation, fibroblast proliferation and the accumulation of extracellular matrix in lung tissues. The dysregulation of lncRNAs and miRNAs has been implicated in many complex diseases; however, the current understanding of their roles in fibrotic lung diseases, especially silicosis, remains limited. Our previous microRNA (miRNA, miR) microarray data have indicated decreased expression levels of miR-489 in lung tissues of silica-induced pulmonary fibrosis. Here, we further explored the role of miR-489 in a mouse model of silicosis. Interestingly, miR-489 levels were reduced in both macrophages that were exposed to silica and fibroblasts that were exposed to TGF-β1. Additionally, the overexpressed miR-489 carried out its anti-fibrotic role by attenuating inflammation and fibrotic progression in vivo. Our molecular study further demonstrated that miR-489 inhibited silica-induced pulmonary fibrosis primarily by repressing its target genes MyD88 and Smad3. Moreover, the up-regulated lncRNA cardiac hypertrophy-related factor (CHRF) reversed the inhibitory effect of miR-489 on MyD88 and Smad3 and then triggered the inflammation and fibrotic signaling pathways. Overall, our data indicate that the CHRF-miR-489-MyD88 Smad3 signaling axis exerts key functions in silica-induced pulmonary fibrosis and may represent a therapeutic target for silicosis.
authors: Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Qiuyun
authors: Q
authors: Wu
authors: Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.|Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.
authors: Lei
authors: L
authors: Han
authors: Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Weiwen
authors: W
authors: Yan
authors: Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Xiaoming
authors: X
authors: Ji
authors: Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Ruhui
authors: R
authors: Han
authors: Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Jingjin
authors: J
authors: Yang
authors: Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Jiali
authors: J
authors: Yuan
authors: Department of Occupational Medicine and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, China.
authors: Chunhui
authors: C
authors: Ni
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000473:pathology; D005786:Gene Expression Regulation; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012822:Silicon Dioxide / Q000633:toxicity; D051900:Smad3 Protein / Q000235:genetics* / Q000378:metabolism; D054645:Protein Phosphatase 1
chemical_list: D000943:Antigens, Differentiation; D035683:MicroRNAs; D009363:Neoplasm Proteins; D062085:RNA, Long Noncoding; D012822:Silicon Dioxide; D051900:Smad3 Protein; C570982:MIRN489 microRNA, mouse; C497791:Smad3 protein, mouse; C513256:Ppp1r15a protein, mouse; D054645:Protein Phosphatase 1