Metformin Triggers Apoptosis and Induction of the G0/G1 Switch 2 Gene in Macrophages.
Animals
Anti-Inflammatory Agents, Non-Steroidal
/ administration & dosage
Apoptosis
/ drug effects
Cell Cycle Proteins
/ genetics
Cell Line
Chickens
Dose-Response Relationship, Drug
Gene Expression Regulation
/ drug effects
Macrophages
/ drug effects
Metformin
/ administration & dosage
Mice
RAW 264.7 Cells
Bcl-2
G0S2
apoptosis
macrophages
metformin
Journal
Genes
ISSN: 2073-4425
Titre abrégé: Genes (Basel)
Pays: Switzerland
ID NLM: 101551097
Informations de publication
Date de publication:
17 09 2021
17 09 2021
Historique:
received:
17
08
2021
revised:
14
09
2021
accepted:
16
09
2021
entrez:
28
9
2021
pubmed:
29
9
2021
medline:
16
2
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34573418
pii: genes12091437
doi: 10.3390/genes12091437
pmc: PMC8468785
pii:
doi:
Substances chimiques
Anti-Inflammatory Agents, Non-Steroidal
0
Cell Cycle Proteins
0
G0S2 protein, mouse
0
Metformin
9100L32L2N
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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