| First Author | Gong Y | Year | 2023 |
| Journal | Mol Med | Volume | 29 |
| Issue | 1 | Pages | 157 |
| PubMed ID | 37953295 | Mgi Jnum | J:343199 |
| Mgi Id | MGI:7564393 | Doi | 10.1186/s10020-023-00750-2 |
| Citation | Gong Y, et al. (2023) USP38 exacerbates atrial inflammation, fibrosis, and susceptibility to atrial fibrillation after myocardial infarction in mice. Mol Med 29(1):157 |
| abstractText | 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-kappaB signaling pathway in the atria was significantly activated after MI, and phosphorylated TAK1, P65, and IkappaBalpha protein expression was significantly upregulated. USP38-CKO inhibited the activation of the TAK1/NF-kappaB signaling pathway, whereas USP38-TG overactivated the TAK1/NF-kappaB signaling pathway after MI. USP38 is dependent on the TAK1/NF-kappaB 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. |
