title: The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis.
abstract: To identify microRNAs (miRNAs, miRs) with potential roles in lung fibrogenesis, we performed genome-wide profiling of miRNA expression in lung tissues from a silica-induced mouse model of pulmonary fibrosis using microarrays. Seventeen miRNAs were selected for validation via qRT-PCR based on the fold changes between the silica and the control group. The dysregulation of five miRNAs, including miR-21, miR-455, miR-151-3p, miR-486-5p and miR-3107, were confirmed by qRT-PCRs in silica-induced mouse model of pulmonary fibrosis and were also confirmed in a bleomycin (BLM)-induced mouse lung fibrosis. Notably, miR-486-5p levels were decreased in the serum samples of patients with silicosis, as well as in the lung tissues of patients with silicosis and idiopathic pulmonary fibrosis (IPF). In addition, as determined by luciferase assays and Western blotting, SMAD2, a crucial mediator of pulmonary fibrosis, was identified to be one of target genes of miR-486-5p. To test the potential therapeutic significance of this miRNA, we overexpressed miR-486-5p in animal models. At day 28, miR-486-5p expression significantly decreased both the distribution and severity of lung lesions compared with the silica group (P < 0.01). In addition, miR-486-5p had a similar effect in the BLM group (P < 0.001). These results indicate that miR-486-5p may inhibit fibrosis.
authors.affiliation: Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Baiqun
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Ruhui
authors.initials: R
authors.lastname: Han
authors.affiliation: Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Jingjin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China.|Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Han
authors.affiliation: Institute of Occupational Disease Prevention, Jiangsu Provincial Center for Disease Control and Prevention, China.
authors.forename: Baoli
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Nanjing Medical University, Affiliated Wuxi People's Hospital, Lung Transplantation Center, Jiangsu Key Laboratory of Organ Transplantation, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wei
authors.affiliation: Nanjing Medical University, Affiliated Wuxi People's Hospital, Lung Transplantation Center, Jiangsu Key Laboratory of Organ Transplantation, China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Ni
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D011658:Pulmonary Fibrosis / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D012829:Silicosis / Q000235:genetics / Q000473:pathology; D051899:Smad2 Protein / Q000737:chemistry / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D035683:MicroRNAs; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1