MiR-26a-5p from HucMSC-derived extracellular vesicles inhibits epithelial mesenchymal transition by targeting Adam17 in silica-induced lung fibrosis

• Published in: Ecotoxicology and environmental safety Vol. 257; p. 114950
• Main Authors: Zhao, Jing, Jiang, Qiyue, Xu, Chunjie, Jia, Qiyue, Wang, Hongwei, Xue, Wenming, Wang, Yan, Zhu, Zhonghui, Tian, Lin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.06.2023; Elsevier
• Subjects: Adam17; ADAM17 Protein - genetics; Animals; EMT; Epithelial-Mesenchymal Transition; Extracellular Vesicles - genetics; Extracellular Vesicles - metabolism; Fibrosis; HucMSC-EVs; Humans; Lung fibrosis; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; MiR-26a-5p; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - genetics; Silica; Silicon Dioxide - toxicity; Silicosis - genetics; EVs; H&E; Adam17; EMT; Silica; Lung fibrosis; 3D; α-SMA; HucMSC-EVs; miRNA; TGF-β1; MiR-26a-5p; ZO1
• ISSN: 0147-6513; 1090-2414
• DOI: 10.1016/j.ecoenv.2023.114950

Silicosis is one of several potentially fatal occupational pathologies caused by the prolonged inhalation of respirable crystalline silica. Previous studies have shown that lung epithelial-mesenchymal transition (EMT) plays a significant role in the fibrosis effect of silicosis. Human umbilical cord mesenchymal stem cells-derived Extracellular vesicles (hucMSC-EVs) have attracted great interest as a potential therapy of EMT and fibrosis-related diseases. However, the potential effects of hucMSC-EVs in inhibiting EMT in silica-induced fibrosis, as well as its underlying mechanisms, remain largely unknown. In this study, we used the EMT model in MLE-12 cells and observed the effects and mechanism of hucMSC-EVs inhibition of EMT. The results revealed that hucMSC-EVs can indeed inhibit EMT. MiR-26a-5p was highly enriched in hucMSC-EVs but was down-regulated in silicosis mice. We found that miR-26a-5p in hucMSC-EVs was over-expressed after transfecting miR-26a-5p expressing lentivirus vectors into hucMSCs. Subsequently, we explored if miR-26a-5p, attained from hucMSC-EVs, was involved in inhibiting EMT in silica-induced lung fibrosis. Our findings suggested that hucMSC-EVs could deliver miR-26a-5p into MLE-12 cells and cause the inhibition of the Adam17/Notch signalling pathway to ameliorate EMT in silica-induced pulmonary fibrosis. These findings might represent a novel insight into treating silicosis fibrosis. [Display omitted] •HucMSC-EVs may be a candidate therapeutic carrier in silicosis.•HucMSC-EVs suppressed the EMT in silica-induced lung fibrosis.•MiR-26a-5p from hucMSC-EVs inhibited the silica-induced EMT through targeting Adam17.