Impact of N-acetyltransferase 10 on macrophage activation and inflammation-induced cardiac dysfunction
Abstract Inflammation-induced cardiac dysfunction, driven by an abnormal immune response, significantly contributes to sepsis-related mortality. Controlling excessive pro-inflammatory cytokine production by immune cells remains a significant challenge. This study investigated the role of N-acetyltra...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-07-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07796-6 |
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| author | Zilong Xiao Xiang Wei Peng Li Ruizhen Chen Ziqing Yu Yixiu Liang Yangang Su Junbo Ge |
| author_facet | Zilong Xiao Xiang Wei Peng Li Ruizhen Chen Ziqing Yu Yixiu Liang Yangang Su Junbo Ge |
| author_sort | Zilong Xiao |
| collection | DOAJ |
| description | Abstract Inflammation-induced cardiac dysfunction, driven by an abnormal immune response, significantly contributes to sepsis-related mortality. Controlling excessive pro-inflammatory cytokine production by immune cells remains a significant challenge. This study investigated the role of N-acetyltransferase 10 (NAT10) in macrophage activation and its contribution to inflammation-induced cardiac dysfunction. Using bone marrow-derived macrophages and an endotoxemia mouse model, we found that NAT10 is significantly upregulated in response to lipopolysaccharide (LPS) due to the deubiquitinating enzyme USP39, which stabilizes the NAT10 protein. ac4C RNA sequencing identified ETS2 as a direct target of NAT10, where the ac4C modification enhanced ETS2 mRNA stability and translation, promoting a pro-inflammatory phenotype in macrophages. NAT10 deficiency reduces LPS-induced macrophage activation and cytokine production, improving cardiac function in mice. Pharmacological inhibition of NAT10 using remodelin produced similar protective effects. Our findings reveal a novel post-transcriptional pathway and highlight the therapeutic potential of targeting NAT10 to mitigate inflammation-induced cardiac injury in endotoxemia |
| format | Article |
| id | doaj-art-de886d42ece9458886517b03e59f1c27 |
| institution | Kabale University |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-de886d42ece9458886517b03e59f1c272025-08-20T03:42:00ZengNature Publishing GroupCell Death and Disease2041-48892025-07-0116111410.1038/s41419-025-07796-6Impact of N-acetyltransferase 10 on macrophage activation and inflammation-induced cardiac dysfunctionZilong Xiao0Xiang Wei1Peng Li2Ruizhen Chen3Ziqing Yu4Yixiu Liang5Yangang Su6Junbo Ge7Department of Cardiology, Zhongshan Hospital, Fudan UniversityInstitute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, Ludwig-Maximilians-Universität MünchenDepartment of Anesthesiology, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, Zhongshan Hospital, Fudan UniversityDepartment of Cardiology, Zhongshan Hospital, Fudan UniversityAbstract Inflammation-induced cardiac dysfunction, driven by an abnormal immune response, significantly contributes to sepsis-related mortality. Controlling excessive pro-inflammatory cytokine production by immune cells remains a significant challenge. This study investigated the role of N-acetyltransferase 10 (NAT10) in macrophage activation and its contribution to inflammation-induced cardiac dysfunction. Using bone marrow-derived macrophages and an endotoxemia mouse model, we found that NAT10 is significantly upregulated in response to lipopolysaccharide (LPS) due to the deubiquitinating enzyme USP39, which stabilizes the NAT10 protein. ac4C RNA sequencing identified ETS2 as a direct target of NAT10, where the ac4C modification enhanced ETS2 mRNA stability and translation, promoting a pro-inflammatory phenotype in macrophages. NAT10 deficiency reduces LPS-induced macrophage activation and cytokine production, improving cardiac function in mice. Pharmacological inhibition of NAT10 using remodelin produced similar protective effects. Our findings reveal a novel post-transcriptional pathway and highlight the therapeutic potential of targeting NAT10 to mitigate inflammation-induced cardiac injury in endotoxemiahttps://doi.org/10.1038/s41419-025-07796-6 |
| spellingShingle | Zilong Xiao Xiang Wei Peng Li Ruizhen Chen Ziqing Yu Yixiu Liang Yangang Su Junbo Ge Impact of N-acetyltransferase 10 on macrophage activation and inflammation-induced cardiac dysfunction Cell Death and Disease |
| title | Impact of N-acetyltransferase 10 on macrophage activation and inflammation-induced cardiac dysfunction |
| title_full | Impact of N-acetyltransferase 10 on macrophage activation and inflammation-induced cardiac dysfunction |
| title_fullStr | Impact of N-acetyltransferase 10 on macrophage activation and inflammation-induced cardiac dysfunction |
| title_full_unstemmed | Impact of N-acetyltransferase 10 on macrophage activation and inflammation-induced cardiac dysfunction |
| title_short | Impact of N-acetyltransferase 10 on macrophage activation and inflammation-induced cardiac dysfunction |
| title_sort | impact of n acetyltransferase 10 on macrophage activation and inflammation induced cardiac dysfunction |
| url | https://doi.org/10.1038/s41419-025-07796-6 |
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