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Updated: Oct 23, 2025
Establishing a Silicosis Rat Model via Exposure of Whole-Body to Respirable Silica
Published on: October 28, 2022
Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling
Demin Cheng1, Qi Xu1, Yue Wang1
1Department of Occupational Medical and Environmental Health, Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
Background:
Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis.
Methods:
The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. Silicon dioxide (SiO2)-stimulated lung epithelial cells/macrophages and transforming growth factor-beta 1 (TGF-β1)-induced differentiated lung fibroblasts were used for in vitro models.
Results:
At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2-10 mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-β1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway.
Conclusions:
In this study, we identified that metformin might be a potential drug for silicosis treatment.
Insights
Metformin shows promise in treating silicosis, a lung fibrosis caused by silica exposure. This study found metformin reduced lung inflammation and fibrosis in mice, suggesting its potential as a therapeutic agent.
Area of Science:
- Pulmonary Medicine
- Pharmacology
- Toxicology
Background:
- Silicosis is a prevalent occupational pulmonary fibrosis with no effective treatments.
- Metformin, an antidiabetic drug, activates AMP-activated protein kinase (AMPK), suggesting potential therapeutic applications.
- This study investigates metformin's efficacy in mitigating silica-induced lung fibrosis.
Purpose of the Study:
- To evaluate the anti-fibrotic effects of metformin in a silica-induced lung fibrosis model.
- To explore the underlying mechanisms of metformin's action in lung epithelial cells, macrophages, and fibroblasts.
Main Methods:
- An in vivo mouse model of silica-induced lung fibrosis (50 mg/kg silica).
- In vitro studies using silica-stimulated lung epithelial cells (A549, HBE) and macrophages (THP-1).
- Transforming growth factor-beta 1 (TGF-β1)-induced lung fibroblasts (MRC-5) were used to assess anti-fibrotic activity.
Main Results:
- Metformin (300 mg/kg) significantly reduced lung inflammation and fibrosis in mice at both early and late stages.
- In vitro, metformin (2-10 mM) reversed silica-induced cytotoxicity, oxidative stress, and epithelial-mesenchymal transition.
- Metformin inhibited macrophage inflammation and alleviated TGF-β1-induced fibroblast activation via an AMPK-dependent pathway.
Conclusions:
- Metformin demonstrates significant anti-fibrotic and anti-inflammatory effects in silica-induced lung injury.
- The findings suggest metformin is a potential therapeutic candidate for treating silicosis.
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