Key Laboratory of Environmental Stress and Chronic Disease Control and Prevention, Ministry of Education, China Medical University, Shenyang, China; Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, China.
Division of Pneumoconiosis, School of Public Health, China Medical University, Shenyang, China.
Ecotoxicol Environ Saf. 2024 Sep 15;283:116971. doi: 10.1016/j.ecoenv.2024.116971. Epub 2024 Aug 30.
Silicosis is an irreversible interstitial lung fibrosis resulting from persistent inflammation induced by long-term inhalation of SiO dust. Treatment and early diagnosis are extremely challenging due to the lack of specific targets and biomarkers. MiRNAs play an important role in the early diagnosis and treatment of various diseases, due to their stability, small variations, and easy detection. Exosomes have become fashionable candidates to deliver miRNAs. However, the specific role of exosomes-loaded miRNAs in silicosis inflammation and fibrosis remains unclear. In the present study, the expression profile of serum exosomal miRNAs in the peripheral blood of silicosis patients was determined by transcritome sequencing. MiR-23a-3p was recognized as a protector against silicosis by bioinformatic analysis. The expression and regulatory axis of miR-23a-3p and its predicted target gene CUL3 were then confirmed. The therapeutic role of the miR-23a-3p/CUL3 axis and its alleviating effect on SiO-induced apoptosis were verified in mice and in epithelial cells. Furthermore, the communication of exosomes carrying miR-23a-3p between macrophages and epithelial cells was demonstrated using a cell co-culture model. Our results suggest that exosomal miR-23a-3p could be prospective as a biomarker in early diagnose for SiO-induced lung fibrosis, and provided new threads for the treatment of silicosis.
硅肺是一种由长期吸入 SiO 粉尘引起的持续性炎症导致的不可逆转的间质性肺纤维化。由于缺乏特定的靶点和生物标志物，治疗和早期诊断极具挑战性。miRNAs 在各种疾病的早期诊断和治疗中发挥着重要作用，这是由于它们的稳定性、微小变化和易于检测。外泌体已成为递送 miRNAs 的热门候选物。然而，外泌体负载的 miRNAs 在矽肺炎症和纤维化中的具体作用仍不清楚。在本研究中，通过转录组测序确定了矽肺患者外周血血清外泌体 miRNAs 的表达谱。通过生物信息学分析，miR-23a-3p 被认为是矽肺的保护因子。然后验证了 miR-23a-3p 及其预测靶基因 CUL3 的表达和调控轴。在小鼠和上皮细胞中验证了 miR-23a-3p/CUL3 轴的治疗作用及其对 SiO 诱导的细胞凋亡的缓解作用。此外，还使用细胞共培养模型证明了携带 miR-23a-3p 的外泌体在巨噬细胞和上皮细胞之间的通讯。我们的研究结果表明，外泌体 miR-23a-3p 可能成为 SiO 诱导肺纤维化早期诊断的有前途的生物标志物，并为矽肺的治疗提供了新的思路。
