Bone Marrow Mesenchymal Stem Cell-Derived Exosomes microRNA-31-5p Repress Pulmonary Fibrosis via IGFBP7

Abstract

Bone marrow mesenchymal stem cell-derived exosomes (BMSCs-Exos) with their molecular cargo have therapeutic potential for pulmonary fibrosis (PF). This research was performed to uncover how microRNA-31-5p (miR-31-5p), carried by BMSCs-Exos, affects PF via modulating IGFBP7. C57BL/6 mice were treated with bleomycin (BLM) to induce PF. Pulmonary function was tested, and fibrotic changes in the mouse lung tissues were examined. Levels of fibrosis-related inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6, were tested. Mouse BMSCs were isolated and identified, and BMSCs-Exos were obtained by ultracentrifugation. Exosome morphology was observed by transmission electron microscopy, the surface markers were measured, and the expression levels of BMSCs-Exo marker proteins were assessed. The targeting relation between miR-31-5p and IGFBP7 was assessed, and the expression of both was tested. After modeling, mice exhibited decreased functional residual capacity, lung compliance, inspiratory capacity, vital capacity, total lung capacity, and forced vital capacity. After 14 days of BLM induction, thickening of the main tracheal wall, fibroblast accumulation, immune cell infiltration in lung interstitium, and increased collagen deposition were observed. Elevated levels of TNF-α, IL-1β, and IL-6 were also noted. BMSCs-Exos attenuated BLM-induced PF, and BMSCs-Exo-derived miR-31-5p ameliorated PF in mice. miR-31-5p was shown to target IGFBP7, diminishing both transcript and protein levels. IGFBP7 overexpression reversed the ameliorative impact of miR-31-5p on PF in mice. BMSCs-Exos ameliorate PF development by delivering miR-31-5p to repress IGFBP7.