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Journal of Translational Medicine

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Open Access 01-12-2021 | Silicosis | Research

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Authors: Demin Cheng, Qi Xu, Yue Wang, Guanru Li, Wenqing Sun, Dongyu Ma, Siyun Zhou, Yi Liu, Lei Han, Chunhui Ni

Published in: Journal of Translational Medicine | Issue 1/2021

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.

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Title: Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling
Authors: Demin Cheng
Qi Xu
Yue Wang
Guanru Li
Wenqing Sun
Dongyu Ma
Siyun Zhou
Yi Liu
Lei Han
Chunhui Ni
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Silicosis
Metformin
Published in: Journal of Translational Medicine / Issue 1/2021
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-021-03036-5

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