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

Institute of Epigenetics and Epigenomics, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China
Department of Animal Science, McGill University, Montréal, QC H3A 0G4, Canada
Department of Pharmacy, Suzhou Vocational Health College, Suzhou 215009, China
Joint International Research Laboratory of Agricultural & Agri-Product Safety, Ministry of Education of China, Yangzhou University, Yangzhou 225009, China
Jiangsu Co-Innovation Center for Prevention & Control of Important Animal Infectious Diseases & Zoonoses, Yangzhou 225009, China
Authors to whom correspondence should be addressed.
Academic Editor: Paula Soares
Genes 2021, 12(9), 1437;
Received: 17 August 2021 / Revised: 14 September 2021 / Accepted: 16 September 2021 / Published: 17 September 2021
(This article belongs to the Section Animal Genetics and Genomics)
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. View Full-Text
Keywords: macrophages; metformin; apoptosis; G0S2; Bcl-2 macrophages; metformin; apoptosis; G0S2; Bcl-2
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MDPI and ACS Style

Hu, X.; Luo, H.; Dou, C.; Chen, X.; Huang, Y.; Wang, L.; Xue, S.; Sun, Z.; Chen, S.; Xu, Q.; Geng, T.; Zhao, X.; Cui, H. Metformin Triggers Apoptosis and Induction of the G0/G1 Switch 2 Gene in Macrophages. Genes 2021, 12, 1437.

AMA Style

Hu X, Luo H, Dou C, Chen X, Huang Y, Wang L, Xue S, Sun Z, Chen S, Xu Q, Geng T, Zhao X, Cui H. Metformin Triggers Apoptosis and Induction of the G0/G1 Switch 2 Gene in Macrophages. Genes. 2021; 12(9):1437.

Chicago/Turabian Style

Hu, Xuming, Huan Luo, Chunfeng Dou, Xujing Chen, Yi Huang, Liping Wang, Songlei Xue, Zhen Sun, Shihao Chen, Qi Xu, Tuoyu Geng, Xin Zhao, and Hengmi Cui. 2021. "Metformin Triggers Apoptosis and Induction of the G0/G1 Switch 2 Gene in Macrophages" Genes 12, no. 9: 1437.

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