OGT-mediated O-GlcNAcylation regulates macrophage polarization in heart failure via targeting IRF1

Abstract Background Heart failure (HF) is a syndrome with complex etiology and high mortality in the world. Macrophage-related inflammation is involved in HF development. O-GlcNAcylation is a post-translational modification that affects pathological processes. This study aimed to investigate the rol...

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Bibliographic Details
Main Authors: Guoqiang Jing, Yuhong Ma
Format: Article
Language:English
Published: BMC 2024-12-01
Series:BMC Cardiovascular Disorders
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Online Access:https://doi.org/10.1186/s12872-024-04429-2
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Summary:Abstract Background Heart failure (HF) is a syndrome with complex etiology and high mortality in the world. Macrophage-related inflammation is involved in HF development. O-GlcNAcylation is a post-translational modification that affects pathological processes. This study aimed to investigate the role of O-GlcNAcylation in HF, especially its effect on macrophage polarization. Methods Raw264.7 cells were treated with lipopolysaccharide (LPS) to induce pro-inflammatory macrophages. HF mice were generated by transverse aortic constriction (TAC). After knockdown of OGT or overexpressing IRF1, macrophage polarization was evaluated using quantitative real-time polymerase chain reaction and flow cytometry. Underlying mechanism was analyzed using bioinformatic analysis, co-immunoprecipitation (co-IP), IP, and western blotting. Results The results showed that O-GlcNAcylation and OGT levels were high in LPS-treated Raw264.7 cells. OGT knockdown inhibited pro-inflammatory macrophage polarization and promoted anti-inflammatory macrophage polarization caused by LPS, and alleviated TAC-induced cardiac dysfunction and fibrosis. Mechanistically, OGT silence suppressed O-GlcNAcylation of IRF1 at Ser (S)283 site. IRF1 overexpression reversed macrophage polarization modulated by OGT knockdown. Conclusion Silencing of OGT promotes macrophage polarization from pro-inflammatory to anti-inflammatory phenotype to alleviate HF through O-GlcNAcylation of IRF1. The findings suggest that O-GlcNAcylation has the potential to treat HF.
ISSN:1471-2261