Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling.

Abstract

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.

• Authors: Demin Cheng, Qi Xu, Yue Wang, Guanru Li, Wenqing Sun, Dongyu Ma, Siyun Zhou, Yi Liu, Lei Han, Chunhui Ni
• Journal: Journal of translational medicine (J Transl Med) Vol. 19 Issue 1 Pg. 349 (08 16 2021) ISSN: 1479-5876 [Electronic] England
• PMID: 34399790 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s).

Chemical References

• Transforming Growth Factor beta1
• Silicon Dioxide
• Metformin
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases
• Animals
• Epithelial-Mesenchymal Transition
• Fibroblasts
• Humans
• Lung
• Metformin (pharmacology, therapeutic use)
• Mice
• Mice, Inbred C57BL
• Pulmonary Fibrosis (chemically induced, drug therapy)
• Silicon Dioxide (toxicity)
• Transforming Growth Factor beta1