MiR-148a-3p Loaded Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Alleviates Silica-Induced Pulmonary Fibrosis by Inhibiting β-Catenin Signaling

作者：Qiyue Jiang, Fuao Ning, Qiyue Jia, Hongwei Wang, Wenming Xue, Jiaxin Wang, Yan Wang, Zhonghui Zhu, Lin Tian · 发表于：International Journal of Nanomedicine · 年份：2025 · DOI：10.2147/ijn.s506542 · 被引用次数：8 · 研究领域：Extracellular vesicles in disease、Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis、Neonatal Respiratory Health Research

Background: In clinical practice, due to the lack of typical symptoms and specific diagnostic biomarkers, silicotic patients often having already developed pulmonary fibrosis by the time of clinical diagnosis. Studies have demonstrated that human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) could moderate silicosis fibrosis, which may be related to the microRNAs (miRNAs) in hucMSC-EVs. While the full extent of their antifibrotic effects and the underlying mechanisms remain to be elucidated. Methods: HucMSC-EVs were administered from day 28 to day 56 after silica exposure in mice, which in a therapeutic manner. In addition, the antifibrotic abilities of engineered hucMSC-EVs with varying levels of miR-148a-3p, a miRNA with antifibrotic properties, were evaluated. Heat shock protein 90 beta family member 1 (Hsp90b1) is reported to be a target of miR-148a-3p, the protein-protein interaction analysis was used to explore its regulated downstream factors in lung fibrosis. The underlying mechanisms were also investigated by using miR-148a-3p mimics and small interfering RNA (siRNA) targeting Hsp90b1 in vitro. Results: HucMSC-EVs could reduce the histopathological changes and the levels of fibrotic proteins in the mouse lung tissues when administered in a therapeutic manner. Meanwhile, miR-148a-3p-overexpressed hucMSC-EVs intervention exhibited the enhanced anti-fibrotic effect compared with the negative control intervention group. In vitro, the el...