Related Experiment Video
Updated: Jun 29, 2025
Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica
Published on: October 28, 2022
The inhibition of MARCO by PolyG alleviates pulmonary fibrosis via regulating mitochondrial function in a silicotic
Meiyu Chang1,2, Ning Li1, Qiang Zhou1
1School of Public Health, North China University of Science and Technology, Tangshan, China.
Abstract:
Silicon dioxide (SiO2)-induced pulmonary fibrosis is potentially associated with the impairment of mitochondrial function. Previous research found that inhibition of macrophage receptor with collagenous structure (MARCO) could alleviate particle-induced lung injury by regulating phagocytosis and mitigating mitochondrial damage. The present study aims to explore the underlying anti-fibrosis mechanism of polyguanylic acid (PolyG, MARCO inhibitor) in a silicotic rat model. Hematoxylin and eosin and Masson staining were performed to visualize lung tissue pathological changes. Confocal microscopy, transmission electron microscope, western blot analysis, quantitative real-time PCR (qPCR), and adenosine triphosphate (ATP) content assay were performed to evaluate collagen content, mitochondrial function, and morphology changes in SiO2-induced rat pulmonary fibrosis. The results suggested that SiO2 exposure contributed to reactive oxygen species aggregation and the reduction of respiratory complexes and ATP synthesis. PolyG treatment could effectively reduce MARCO expression and ameliorate lung injury and fibrosis by rectifying the imbalance of mitochondrial respiration and energy synthesis. Furthermore, PolyG could maintain mitochondrial homeostasis by promoting peroxisome proliferator-activated receptor-coactivator 1 α (PGC1α)-mediated mitochondrial biogenesis and regulating fusion and fission. Together, PolyG could ameliorate SiO2-induced pulmonary fibrosis via inhibiting MARCO to protect mitochondrial function.
Insights
Polyguanylic acid (PolyG) protects against silica-induced pulmonary fibrosis by inhibiting MARCO. This treatment preserves mitochondrial function, reduces lung injury, and promotes mitochondrial biogenesis.
Area of Science:
- Toxicology
- Cell Biology
- Pathology
Background:
- Silicon dioxide (SiO2) exposure can cause pulmonary fibrosis, often linked to mitochondrial dysfunction.
- Macrophage receptor with collagenous structure (MARCO) inhibition shows promise in mitigating particle-induced lung injury.
- Understanding the anti-fibrosis mechanisms of MARCO inhibitors is crucial for developing treatments.
Purpose of the Study:
- To investigate the anti-fibrosis effects of polyguanylic acid (PolyG), a MARCO inhibitor, in a rat model of silicosis.
- To elucidate the role of PolyG in protecting mitochondrial function during silica-induced pulmonary fibrosis.
- To explore the molecular pathways, including mitochondrial biogenesis and dynamics, influenced by PolyG.
Main Methods:
- Silicotic rat model established with SiO2 exposure.
- Histopathological analysis using Hematoxylin and eosin and Masson staining.
- Assessment of mitochondrial function via transmission electron microscopy, western blot, qPCR, and ATP assays.
- Evaluation of MARCO expression and related signaling pathways.
Main Results:
- SiO2 exposure led to increased reactive oxygen species, impaired mitochondrial respiration, and reduced ATP synthesis.
- PolyG treatment significantly reduced MARCO expression, ameliorated lung injury and fibrosis.
- PolyG normalized mitochondrial respiration and energy synthesis, promoting mitochondrial biogenesis via PGC1α and regulating mitochondrial fusion/fission.
Conclusions:
- Polyguanylic acid (PolyG) effectively ameliorates SiO2-induced pulmonary fibrosis.
- Inhibition of MARCO by PolyG protects mitochondrial function and restores energy homeostasis.
- PolyG represents a potential therapeutic strategy for silicosis by targeting MARCO and enhancing mitochondrial health.
