The Anti-fibrotic Effects and Mechanisms of MicroRNA-486-5p in Pulmonary Fibrosis

• DOI: 10.1038/srep14131
• Publication Date: 2015-09-15T10:44:32Z
• Authors: Xiaoming Ji; Baiqun Wu; Jingjing Fan; Ruhui Han; Chen Luo; Ting Wang; Jingjin Yang; Lei Han; Baoli Zhu; Dong Wei; Jingyu Chen; Chunhui Ni
• Keywords: 0303 health sciences; Binding Sites; Base Sequence; Pulmonary Fibrosis; Silicosis; Down-Regulation; Smad2 Protein; Fibroblasts; Article; 3. Good health; Transforming Growth Factor beta1; Disease Models, Animal; Mice; MicroRNAs; 03 medical and health sciences; Gene Expression Regulation; Animals; Humans; RNA Interference; Lung; Cell Proliferation

AbstractTo 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.