MicroRNA-124-3p alleviates repetitive bleomycin-inducedidiopathic pulmonary fibrosis in mouse by repressing Wnt/β-catenin signaling component AXIN1

Abstract

Background: MicroRNA (miR)-124-3p is a crucial player in the transforming growth factor β1-induced in vitro fibrogenic differentiation of mesenchymal stem cells. In the current study, we aimed to further verify the in vivo role of miR-124-3p in a mouse model of idiopathic pulmonary fibrosis (IPF).Methods: Mouse IPF model was established using repetitive intratracheal bleomycin (BLM) dosing,followed by in vivo delivery of miR-124-3p. Masson’s trichrome staining, hematoxylin-eosin (H&E),and modified Ashcroft score were performed on lung tissues to assess extent of pulmonary fibrosis.Collagen deposition was examined using hydroxyproline assay. Inflammatory cell counts were evaluated in the bronchoalveolar lavage (BAL) fluid. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed to assess apoptosis in lung tissues.Results: Repetitive BLM injection induced elevated fibrosis score and collagen deposition, elevated numbers of inflammatory cells in the BAL fluid, and promoted in lung tissues of mice. MiR-124-3p, to a considerable extent, reversed the BLM-induced IPF symptoms in terms of fibrosis score and collagen deposition in the lung tissues, reduced the BLM-elevated inflammatory cells in the BAL fluid and the percentage of BLM-induced apoptotic cells in lung tissues. AXIN1, a pivotal component in Wnt signaling, was also significantly inhibited by miR-124-3p in the experimental mice.Conclusion: MiR-124-3p serves as a therapeutic target in the mouse model of IPF by repressing Wnt/β-catenin signaling component AXIN1 and holds great clinical potential in molecular therapies to treat human IPF patients.