Metformin Triggers Apoptosis and Induction of the G0/G1 Switch 2 Gene in Macrophages

Metformin is a widely used antidiabetic drug for the treatment of type 2 diabetes and has been recently demonstrated to possess anti-inflammatory properties via AMPK-mediated modulation of M2 macrophage activation. However, the anti-inflammatory mechanisms of metformin on inflammatory macrophages ar...

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Bibliographic Details
Published in:Genes 2021-09, Vol.12 (9), p.1437
Main Authors: Hu, Xuming, Luo, Huan, Dou, Chunfeng, Chen, Xujing, Huang, Yi, Wang, Liping, Xue, Songlei, Sun, Zhen, Chen, Shihao, Xu, Qi, Geng, Tuoyu, Zhao, Xin, Cui, Hengmi
Format: Article
Language:English
Subjects:
Animals
Anti-inflammatory agents
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
Anti-Inflammatory Agents, Non-Steroidal - pharmacology
Apoptosis
Apoptosis - drug effects
Apoptosis - genetics
Bcl-2 protein
Cell activation
Cell Cycle Proteins - genetics
Cell Line
Chickens
Data analysis
Diabetes mellitus (non-insulin dependent)
Dose-Response Relationship, Drug
Flow cytometry
Gene expression
Gene Expression Regulation - drug effects
Genomes
Humidity
Inflammation
Kinases
Macrophages
Macrophages - drug effects
Macrophages - physiology
Metformin
Metformin - administration & dosage
Metformin - pharmacology
Mice
Plasmids
RAW 264.7 Cells
Signal transduction
Software
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Summary:Metformin is a widely used antidiabetic drug for the treatment of type 2 diabetes and has been recently demonstrated to possess anti-inflammatory properties via AMPK-mediated modulation of M2 macrophage activation. However, the anti-inflammatory mechanisms of metformin on inflammatory macrophages are still not fully elucidated. In this study, we found that metformin induced apoptosis in macrophages. In particular, metformin induced apoptosis of M1 macrophages, based on M1 marker genes in apoptotic macrophages. Next, we comprehensively screened metformin-responsive genes in macrophages by RNA-seq and focused on the extrinsic apoptotic signaling pathway. The G0/G1 switch 2 gene (G0S2) was robustly up-regulated by metformin in macrophages. Overexpression of G0S2 significantly induced apoptosis of macrophages in a dose-dependent manner and blunted the function of the crucial anti-apoptotic gene Bcl-2, which was significantly reduced by metformin. These findings show that metformin promoted apoptosis of macrophages, especially M1 macrophages, via G0S2 induction and provides a novel anti-inflammatory mechanism of metformin through induction of macrophage apoptosis.
ISSN:2073-4425
2073-4425
DOI:10.3390/genes12091437