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Updated: Jul 13, 2025
A Silicosis Mouse Model Established by Repeated Inhalation of Crystalline Silica Dust
Published on: January 6, 2023
MiR-148a-3p within HucMSC-Derived Extracellular Vesicles Suppresses Hsp90b1 to Prevent Fibroblast Collagen Synthesis
Qiyue Jiang1,2, Jing Zhao1,2, Qiyue Jia1,2
1Department of Occupational and Environmental Health, School of Public Health, Capital Medical University, Beijing 100069, China.
Abstract:
Silicosis is a fatal occupational respiratory disease caused by the prolonged inhalation of respirable silica. The core event of silicosis is the heightened activity of fibroblasts, which excessively synthesize extracellular matrix (ECM) proteins. Our previous studies have highlighted that human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) hold promise in mitigating silicosis and the significant role played by microRNAs (miRNAs) in this process. Delving deeper into this mechanism, we found that miR-148a-3p was the most abundant miRNA of the differential miRNAs in hucMSC-EVs, with the gene heat shock protein 90 beta family member 1 (Hsp90b1) as a potential target. Notably, miR-148a-3p's expression was downregulated during the progression of silica-induced pulmonary fibrosis both in vitro and in vivo, but was restored after hucMSC-EVs treatment (p < 0.05). Introducing miR-148a-3p mimics effectively hindered the collagen synthesis and secretion of fibroblasts induced by transforming growth factor-β1 (TGF-β1) (p < 0.05). Confirming our hypothesis, Hsp90b1 was indeed targeted by miR-148a-3p, with significantly reduced collagen activity in TGF-β1-treated fibroblasts upon Hsp90b1 inhibition (p < 0.05). Collectively, our findings provide compelling evidence that links miR-148a-3p present in hucMSC-EVs with the amelioration of silicosis, suggesting its therapeutic potential by specifically targeting Hsp90b1, thereby inhibiting fibroblast collagen activities. This study sheds light on the role of miR-148a-3p in hucMSC-EVs, opening avenues for innovative therapeutic interventions targeting molecular pathways in pulmonary fibrosis.
Insights
Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) show promise for treating silicosis. Their miR-148a-3p targets Hsp90b1, reducing fibroblast collagen activity and mitigating pulmonary fibrosis.
Area of Science:
- Biomedical research
- Cell biology
- Occupational health
Background:
- Silicosis is a fatal lung disease caused by silica inhalation, characterized by excessive fibroblast activity and extracellular matrix (ECM) production.
- Human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs) have shown therapeutic potential for silicosis, with microRNAs (miRNAs) playing a key role.
- miR-148a-3p is a key miRNA in hucMSC-EVs, and its expression is reduced in silica-induced pulmonary fibrosis.
Purpose of the Study:
- To investigate the therapeutic mechanism of hucMSC-EVs in silicosis, focusing on the role of miR-148a-3p and its target gene, heat shock protein 90 beta family member 1 (Hsp90b1).
- To explore the potential of miR-148a-3p as a therapeutic agent for pulmonary fibrosis by targeting fibroblast collagen synthesis.
Main Methods:
- Analysis of miRNA expression in hucMSC-EVs and silica-induced pulmonary fibrosis models (in vitro and in vivo).
- Introduction of miR-148a-3p mimics to assess their effect on fibroblast collagen synthesis.
- Validation of Hsp90b1 as a direct target of miR-148a-3p and assessment of collagen activity upon Hsp90b1 inhibition.
Main Results:
- miR-148a-3p was the most abundant differential miRNA in hucMSC-EVs and its expression was downregulated in silicosis, but restored by hucMSC-EVs treatment.
- Overexpression of miR-148a-3p significantly inhibited transforming growth factor-β1 (TGF-β1)-induced fibroblast collagen synthesis and secretion.
- Hsp90b1 was confirmed as a target of miR-148a-3p, and its inhibition reduced collagen activity in TGF-β1-treated fibroblasts.
Conclusions:
- hucMSC-EVs ameliorate silicosis by delivering miR-148a-3p, which targets Hsp90b1 to inhibit fibroblast collagen production.
- miR-148a-3p holds therapeutic potential for silicosis and other fibrotic lung diseases by modulating key molecular pathways.
