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Silicosis of pulmonary fibrosis (PF) is related to long-term excessive inhalation of silica. The activation of fibroblasts into myofibroblasts is the main terminal effect leading to lung fibrosis, which is of great significance to the study of the occurrence and development of silicosis fibrosis and its prevention and treatment. Exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-Exos) are considered to be a potential therapy of silica-induced PF, however, their exact mechanism remains unknown. Therefore, this study aims to explore whether hucMSC-Exos affect the activation of fibroblasts to alleviate PF. In this study, a three-dimensional (3D) method was applied to culture hucMSCs and MRC-5 cells (human embryonic lung fibroblasts), and exosomes were isolated from serum-free media, identified by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM) and Western blotting analysis. Then, the study used an animal model of silica-induced PF to observe the effects of hucMSC-Exos and MRC-5-Exos on activation of fibroblasts. In addition, the activation of fibroblasts was analyzed by Western blotting analysis, wound healing, and migration assay with the treatment of hucMSC-Exos and MRC-5-Exos in NIH-3T3 cells (mouse embryonic fibroblasts). Furthermore, differential expression of microRNAs (DE miRNAs) was measured between hucMSCs-Exos and MRC-5-Exos by high throughput sequence. HucMSC-Exos inhibited the activation of fibroblasts in mice and NIH-3T3 cells. Let-7i-5p was significantly up-regulated in hucMSCs-Exos compared to MRC-5-Exos, which was related to silica-induced PF. Let-7i-5p of hucMSCs-Exos was responsible for the activation of fibroblasts by targeting TGFBR1. Meanwhile, Smad3 was also an important role in the activation of fibroblasts. The study demonstrates that hucMSCs-Exos act as a mediator that transfers let-7i-5p to inhibit the activation of fibroblasts, which alleviates PF through the TGFBR1/Smad3 signaling pathway. The mechanism has potential value for the treatment of silica-induced PF.
Xu et al. (Fri,) studied this question.