The therapeutic effect of exosomal lncRNA MSTRG.91634.7 on mitochondrial dysfunction during SiO-induced lung fibrosis.

Long-term silica (SiO) exposure led to irreversible lung fibrosis, in which epithelial-mesenchymal transition (EMT) played an essential role. A novel lncRNA MSTRG.91634.7 in the peripheral exosomes of silicosis patients was reported in our previous study, which could remold the pathological process of silicosis. However, whether its regulatory role on the development of silicosis was related to EMT process is unclear, and its mechanism remains to be further studied. In this study, up-regulating lncRNA MSTRG91634.7 restricted SiO-activated EMT and restored mitochondrial homeostasis binding to PINK1 in vitro. Moreover, overexpressing PINK1 could inhibit SiO-activated EMT in pulmonary inflammation and fibrosis in mice. Meanwhile, PINK1 contributed to restoring the SiO-induced mitochondrial dysfunction in mice lung. Our results revealed that exosomal lncRNA MSTRG.91634.7 from macrophages could restore mitochondrial homeostasis to restrict the SiO-activated EMT by binding to PINK1 during pulmonary inflammation and fibrosis due to SiO exposure.