The role of miR-497-5p in myofibroblast differentiation of LR-MSCs and pulmonary fibrogenesis

• Published in: Scientific reports 2017-01, Vol.7 (1), p.40958, Article 40958
• Main Authors: Chen, Xiang, Shi, Chaowen, Wang, Cong, Liu, Weilin, Chu, Yanhong, Xiang, Zou, Hu, Kebin, Dong, Ping, Han, Xiaodong
• Format: Article
• Language: English
• Subjects: 38/109; 38/61; 42/100; 42/41; 45; 631/532/1360; 631/80/304; 64; 692/699/1785/4039; 82; 96; Animal models; Animals; Blotting, Western; Cell Differentiation; Cells, Cultured; Chromosome 5; Cysteine; Disease Models, Animal; Fibrosis; Gelatinase A; Gelatinase B; Genes, Reporter; GPI-Linked Proteins - metabolism; Histocytochemistry; Humanities and Social Sciences; Idiopathic Pulmonary Fibrosis - pathology; Immunohistochemistry; Luciferases - analysis; Luciferases - genetics; Lung diseases; Matrix metalloproteinase; Mesenchymal Stromal Cells - physiology; Mesenchyme; Metalloproteinase; Mice; MicroRNAs - metabolism; miRNA; multidisciplinary; Myofibroblasts - physiology; Obstructive lung disease; Pulmonary fibrosis; Reversion; Science; Science (multidisciplinary); Stem cell transplantation; Stem cells; Transforming growth factor; Transforming growth factor-b1
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep40958

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal fibrotic lung disease characterized by profound changes in stem cell differentiation, epithelial cell phenotypes and fibroblast proliferation. In our study, we found that miR-497-5p was significantly upregulated both during myofibroblast differentiation of lung resident mesenchymal stem cells (LR-MSCs) and in the lung tissues of a pulmonary fibrosis model. In addition, as determined by luciferase assays and Western blot analysis, reversion-inducing cysteine-rich protein with kazal motifs ( Reck ) was identified to be one of the target genes of miR-497-5p, and Reck could suppress the expression of matrix metalloproteinase-2 (Mmp2) and Mmp9, which could activate latent transforming growth factor-β1 (TGF-β1). To test the potential therapeutic significance of this miRNA, we modulated the expression of miR-497-5p in LR-MSCs and relevant animal models. The results demonstrated that upregulation of miR-497-5p could induce LR-MSCs to differentiate into myofibroblasts and promote pulmonary fibrogenesis, while inhibition of its expression could effectively retard these processes. In conclusion, our work supports that controlling pulmonary fibrogenesis via inhibition of miR-497-5p expression may provide a potential therapeutic strategy for IPF.