Related Experiment Video
Updated: Feb 19, 2026
Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica
Published on: October 28, 2022
miR-1224-5p Mediates Mitochondrial Damage to Affect Silica-Induced Pulmonary Fibrosis by Targeting BECN1
Qiuyun Wu1,2, Tiantian Xu3, Yi Liu4
1School of Public Health, Xuzhou Medical University, Xuzhou 221004, China. xjwqy922@163.com.
Abstract:
Silicosis is associated with fibroblast proliferation and extracellular matrix deposition in lung tissues. The dysregulation of miR-1224-5p has been implicated in several human cancers; however, the expression and function of miR-1224-5p in silicosis is unknown. The mitochondrial dysfunctions play critical roles in some diseases, but how these processes are regulated in silicosis remains limited. Here, we explored the role of miR-1224-5p in a mouse model of silicosis. We showed that the expression of miR-1224-5p is increased both in lung tissues of silica-induced pulmonary fibrosis and fibroblasts exposed to TGF-β1. Repression of miR-1224-5p expression attenuated silica-induced fibrotic progression in vivo and TGF-β1-induced myofibroblast differentiation in vitro. Additionally, we demonstrated that miR-1224-5p facilitated silica-induced pulmonary fibrosis primarily by repressing one of target genes, BECN1, thereby blocking PARK2 translocation to mitochondria and inducing the accumulation of damaged mitochondria. Furthermore, the activation of PDGFR signal mediated by mitochondrial damage and insufficient mitophagy resulted in myofibroblast differentiation. Collectively, these data indicated that miR-1224-5p exerts key functions in silica-induced pulmonary fibrosis and may represent a potential therapeutic target for silicosis.
Insights
MicroRNA-1224-5p is upregulated in silicosis, promoting lung fibrosis by impairing mitochondrial function and blocking mitophagy. Inhibiting this microRNA may offer a new therapeutic strategy for treating silicosis.
Area of Science:
- Pulmonary Medicine
- Molecular Biology
- Cell Biology
Background:
- Silicosis involves lung fibroblast proliferation and extracellular matrix deposition.
- MicroRNA-1224-5p dysregulation is linked to cancers, but its role in silicosis is unclear.
- Mitochondrial dysfunction is implicated in diseases, with limited understanding in silicosis.
Purpose of the Study:
- To investigate the expression and function of microRNA-1224-5p in a mouse model of silicosis.
- To elucidate the molecular mechanisms by which microRNA-1224-5p influences silica-induced pulmonary fibrosis.
- To assess the therapeutic potential of targeting microRNA-1224-5p for silicosis.
Main Methods:
- Analysis of microRNA-1224-5p expression in silica-induced pulmonary fibrosis mouse models and TGF-β1-stimulated fibroblasts.
- In vivo and in vitro experiments to evaluate the effects of miR-1224-5p repression on fibrotic progression and myofibroblast differentiation.
- Investigation of miR-1224-5p targets, including BECN1, and their role in mitochondrial function, mitophagy, and PDGFR signaling.
Main Results:
- MicroRNA-1224-5p expression was elevated in silica-exposed lung tissues and TGF-β1-treated fibroblasts.
- Repressing miR-1224-5p attenuated silica-induced fibrosis in vivo and myofibroblast differentiation in vitro.
- miR-1224-5p promotes fibrosis by inhibiting BECN1, disrupting PARK2 translocation to mitochondria, causing mitochondrial damage, and activating PDGFR signaling via impaired mitophagy.
Conclusions:
- MicroRNA-1224-5p plays a critical role in silica-induced pulmonary fibrosis.
- The mechanism involves mitochondrial dysfunction and impaired mitophagy, leading to myofibroblast activation.
- MicroRNA-1224-5p represents a potential therapeutic target for silicosis treatment.
