School of Public Health, the Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou 550025, China; Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, Liaoning 110122, China.
Int Immunopharmacol. 2023 Aug;121:110508. doi: 10.1016/j.intimp.2023.110508. Epub 2023 Jun 18.
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.
长期的二氧化硅（SiO）暴露会导致不可逆转的肺纤维化，其中上皮-间充质转化（EMT）起着重要作用。在我们之前的研究中报道了矽肺患者外周细胞外体中的一种新型长链非编码 RNA MSTRG.91634.7，它可以重塑矽肺的病理过程。然而，其对矽肺发展的调节作用是否与 EMT 过程有关尚不清楚，其机制仍有待进一步研究。在这项研究中，上调长链非编码 RNA MSTRG91634.7 在体外通过与 PINK1 结合来限制 SiO 激活的 EMT，并恢复线粒体稳态。此外，过表达 PINK1 可以抑制小鼠肺部炎症和纤维化中 SiO 激活的 EMT。同时，PINK1 有助于恢复 SiO 诱导的小鼠肺线粒体功能障碍。我们的结果表明，巨噬细胞来源的细胞外体长链非编码 RNA MSTRG.91634.7 可以通过与 PINK1 结合恢复线粒体稳态，从而限制 SiO 激活的 EMT，在 SiO 暴露引起的肺部炎症和纤维化过程中。
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