Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, PR China.
Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, PR China; School of Public Health, Jinzhou Medical University, Jinzhou, PR China.
Toxicol Lett. 2023 Jan 1;372:36-44. doi: 10.1016/j.toxlet.2022.10.004. Epub 2022 Oct 26.
Silicosis is a fibrotic lung disease caused by the inhalation of free crystalline silica. Its pathogenesis is extremely complex and involves a variety of cells. Exosomes emerge as a favorable candidate for communication between cells. LncRNA is a major component transported by exosomes in many inflammatory diseases. However, the role of exosomal lncRNA in the pathogenesis of silicosis is still unclear. In this study, the decreased expression of a novel exosomal lncRNA MSTRG.91634.7 in silicosis patients was identified according to high-throughput sequencing. Then, this macrophage-derived exosomal lncRNA MSTRG.91634.7 could regulate the fibroblast's activation by targeting PINK1 in a co-culture system of THP-1 and MRC-5. Finally, the mouse was exposed to 3 mg/50 μL silica to set up the silicosis model. AAV-ov-Pink1 was intratracheally injected to overexpress PINK1 in mice lungs. Our results suggested that PINK1, the target protein of lncRNA MSTRG.91634.7, participated in restricting the silica-induced lung inflammation and fibrosis in mice.
硅肺是一种由游离结晶二氧化硅吸入引起的纤维性肺部疾病。其发病机制极其复杂，涉及多种细胞。外泌体作为细胞间通讯的一个理想候选者出现了。lncRNA 是许多炎症性疾病中外泌体中主要的运输成分。然而，外泌体 lncRNA 在硅肺发病机制中的作用仍不清楚。在这项研究中，根据高通量测序，鉴定了硅肺患者中一种新型外泌体 lncRNA MSTRG.91634.7 的表达下调。然后，这种巨噬细胞来源的外泌体 lncRNA MSTRG.91634.7 可以通过在 THP-1 和 MRC-5 的共培养系统中靶向 PINK1 来调节成纤维细胞的激活。最后，用 3mg/50μl 的二氧化硅对小鼠进行暴露，建立硅肺模型。用 AAV-ov-Pink1 对小鼠肺部进行转染，过表达 PINK1。我们的结果表明，lncRNA MSTRG.91634.7 的靶蛋白 PINK1 参与限制了小鼠二氧化硅诱导的肺部炎症和纤维化。
