USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in mice
Abstract Background Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear. Methods In this...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-023-00750-2 |
| _version_ | 1797558960611393536 |
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| author | Yang Gong Tingting Yu Wei Shuai Tao Chen Jingjing Zhang He Huang |
| author_facet | Yang Gong Tingting Yu Wei Shuai Tao Chen Jingjing Zhang He Huang |
| author_sort | Yang Gong |
| collection | DOAJ |
| description | Abstract Background Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear. Methods In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms. Results Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, and reducing susceptibility to AF on day 7 after MI. USP38-TG showed the opposite effect. Mechanistically, The TAK1/NF-κB signaling pathway in the atria was significantly activated after MI, and phosphorylated TAK1, P65, and IκBα protein expression was significantly upregulated. USP38-CKO inhibited the activation of the TAK1/NF-κB signaling pathway, whereas USP38-TG overactivated the TAK1/NF-κB signaling pathway after MI. USP38 is dependent on the TAK1/NF-κB signaling pathway and regulates atrial inflammation, fibrosis, and arrhythmias after MI to some extent. Conclusions USP38 plays an important role in atrial inflammation, fibrosis, and AF susceptibility after MI, providing a promising target for the treatment of AF after MI. |
| first_indexed | 2024-03-10T17:38:53Z |
| format | Article |
| id | doaj.art-b2bc40eabee44759a33631c7fff66616 |
| institution | Directory Open Access Journal |
| issn | 1528-3658 |
| language | English |
| last_indexed | 2024-03-10T17:38:53Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-b2bc40eabee44759a33631c7fff666162023-11-20T09:46:21ZengBMCMolecular Medicine1528-36582023-11-0129111410.1186/s10020-023-00750-2USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in miceYang Gong0Tingting Yu1Wei Shuai2Tao Chen3Jingjing Zhang4He Huang5Department of Cardiology, Renmin Hospital of Wuhan UniversityDepartment of Respiratory Medicine, Hubei Veterans HospitalDepartment of Cardiology, Renmin Hospital of Wuhan UniversityDepartment of Cardiology, Renmin Hospital of Wuhan UniversityDepartment of Cardiology, Renmin Hospital of Wuhan UniversityDepartment of Cardiology, Renmin Hospital of Wuhan UniversityAbstract Background Inflammation plays an important role in the pathogenesis of atrial fibrillation (AF) after myocardial infarction (MI). The role of USP38, a member of the ubiquitin-specific protease family, on MI-induced atrial inflammation, fibrosis, and associated AF is unclear. Methods In this study, we surgically constructed a mouse MI model using USP38 cardiac conditional knockout (USP38-CKO) and cardiac-specific overexpression (USP38-TG) mice and applied biochemical, histological, electrophysiological characterization and molecular biology to investigate the effects of USP38 on atrial inflammation, fibrosis, and AF and its mechanisms. Results Our results revealed that USP38-CKO attenuates atrial inflammation, thereby ameliorating fibrosis, and abnormal electrophysiologic properties, and reducing susceptibility to AF on day 7 after MI. USP38-TG showed the opposite effect. Mechanistically, The TAK1/NF-κB signaling pathway in the atria was significantly activated after MI, and phosphorylated TAK1, P65, and IκBα protein expression was significantly upregulated. USP38-CKO inhibited the activation of the TAK1/NF-κB signaling pathway, whereas USP38-TG overactivated the TAK1/NF-κB signaling pathway after MI. USP38 is dependent on the TAK1/NF-κB signaling pathway and regulates atrial inflammation, fibrosis, and arrhythmias after MI to some extent. Conclusions USP38 plays an important role in atrial inflammation, fibrosis, and AF susceptibility after MI, providing a promising target for the treatment of AF after MI.https://doi.org/10.1186/s10020-023-00750-2Atrial fibrillationInflammationMyocardial infarctionUbiquitin-specific protease |
| spellingShingle | Yang Gong Tingting Yu Wei Shuai Tao Chen Jingjing Zhang He Huang USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in mice Molecular Medicine Atrial fibrillation Inflammation Myocardial infarction Ubiquitin-specific protease |
| title | USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in mice |
| title_full | USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in mice |
| title_fullStr | USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in mice |
| title_full_unstemmed | USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in mice |
| title_short | USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in mice |
| title_sort | usp38 exacerbates atrial inflammation fibrosis and susceptibility to atrial fibrillation after myocardial infarction in mice |
| topic | Atrial fibrillation Inflammation Myocardial infarction Ubiquitin-specific protease |
| url | https://doi.org/10.1186/s10020-023-00750-2 |
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