Metformin Triggers Apoptosis and Induction of the G0/G1 Switch 2 Gene in Macrophages
| Autor: | Shihao Chen, Xin Zhao, Yi Huang, Huan Luo, Liping Wang, Hu Xuming, Chen Xujing, Tuoyu Geng, Dou Chunfeng, Zhen Sun, Hengmi Cui, Songlei Xue, Qi Xu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
endocrine system diseases
Extrinsic apoptotic signaling pathway Cell Cycle Proteins Type 2 diabetes QH426-470 Article Cell Line Macrophage apoptosis Mice medicine Genetics Animals Bcl-2 Gene Genetics (clinical) G0S2 Dose-Response Relationship Drug Chemistry Anti-Inflammatory Agents Non-Steroidal digestive oral and skin physiology apoptosis nutritional and metabolic diseases M2 Macrophage medicine.disease Metformin macrophages RAW 264.7 Cells Gene Expression Regulation Apoptosis Cancer research metformin Chickens Function (biology) medicine.drug |
| Zdroj: | Genes, Vol 12, Iss 1437, p 1437 (2021) Genes Volume 12 Issue 9 |
| ISSN: | 2073-4425 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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