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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BMC
2024-12-01
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| Series: | BMC Cardiovascular Disorders |
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| Online Access: | https://doi.org/10.1186/s12872-024-04429-2 |
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| author | Guoqiang Jing Yuhong Ma |
| author_facet | Guoqiang Jing Yuhong Ma |
| author_sort | Guoqiang Jing |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8395a359c1fe4b6bacb1f70cca13755d |
| institution | Kabale University |
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| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
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| series | BMC Cardiovascular Disorders |
| spelling | doaj-art-8395a359c1fe4b6bacb1f70cca13755d2025-01-05T12:08:03ZengBMCBMC Cardiovascular Disorders1471-22612024-12-0124111110.1186/s12872-024-04429-2OGT-mediated O-GlcNAcylation regulates macrophage polarization in heart failure via targeting IRF1Guoqiang Jing0Yuhong Ma1Department of Cardiovascular Medicine, The Affiliated Hospital of Inner Mongolia Medical UniversityDepartment of General Medicine, The Affiliated Hospital of Inner Mongolia Medical UniversityAbstract 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.https://doi.org/10.1186/s12872-024-04429-2O-GlcNAcylationPro-/anti-inflammatory macrophageOGTIRF2Heart failureLipopolysaccharide |
| spellingShingle | Guoqiang Jing Yuhong Ma OGT-mediated O-GlcNAcylation regulates macrophage polarization in heart failure via targeting IRF1 BMC Cardiovascular Disorders O-GlcNAcylation Pro-/anti-inflammatory macrophage OGT IRF2 Heart failure Lipopolysaccharide |
| title | OGT-mediated O-GlcNAcylation regulates macrophage polarization in heart failure via targeting IRF1 |
| title_full | OGT-mediated O-GlcNAcylation regulates macrophage polarization in heart failure via targeting IRF1 |
| title_fullStr | OGT-mediated O-GlcNAcylation regulates macrophage polarization in heart failure via targeting IRF1 |
| title_full_unstemmed | OGT-mediated O-GlcNAcylation regulates macrophage polarization in heart failure via targeting IRF1 |
| title_short | OGT-mediated O-GlcNAcylation regulates macrophage polarization in heart failure via targeting IRF1 |
| title_sort | ogt mediated o glcnacylation regulates macrophage polarization in heart failure via targeting irf1 |
| topic | O-GlcNAcylation Pro-/anti-inflammatory macrophage OGT IRF2 Heart failure Lipopolysaccharide |
| url | https://doi.org/10.1186/s12872-024-04429-2 |
| work_keys_str_mv | AT guoqiangjing ogtmediatedoglcnacylationregulatesmacrophagepolarizationinheartfailureviatargetingirf1 AT yuhongma ogtmediatedoglcnacylationregulatesmacrophagepolarizationinheartfailureviatargetingirf1 |