title: The role of miR-497-5p in myofibroblast differentiation of LR-MSCs and pulmonary fibrogenesis.
abstract: 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.
authors.affiliation: Immunology and Reproduction Biology Laboratory &State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Chen
authors.affiliation: Immunology and Reproduction Biology Laboratory &State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China.
authors.forename: Chaowen
authors.initials: C
authors.lastname: Shi
authors.affiliation: Immunology and Reproduction Biology Laboratory &State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Immunology and Reproduction Biology Laboratory &State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Liu
authors.affiliation: Immunology and Reproduction Biology Laboratory &State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
authors.forename: Zou
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: Department of Medicine, Division of Nephrology, Penn State University College of Medicine, Hershey, 17033, Pennsylvania, USA.
authors.forename: Kebin
authors.initials: K
authors.lastname: Hu
authors.affiliation: Immunology and Reproduction Biology Laboratory &State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Dong
authors.affiliation: Immunology and Reproduction Biology Laboratory &State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China.|Jiangsu Key Laboratory of Molecular Medicine, Nanjing, 210093, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Han
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D058851:GPI-Linked Proteins / Q000378:metabolism*; D017930:Genes, Reporter; D006651:Histocytochemistry; D054990:Idiopathic Pulmonary Fibrosis / Q000473:pathology*; D007150:Immunohistochemistry; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D058628:Myofibroblasts / Q000502:physiology*
chemical_list: D058851:GPI-Linked Proteins; D035683:MicroRNAs; C492025:Reck protein, mouse; C550139:mirn497 microRNA, mouse; D008156:Luciferases