A20 (TNFAIP3) alleviates viral myocarditis through ADAR1/miR-1a-3p-dependent regulation
Abstract Objective To investigate the effect of A20 and how A20 is regulated in viral myocarditis (VMC). Methods BABL/C mice, primary neonatal rat cardiomyocytes and H9c2 cells were infected with Coxsackie virus B3 (CVB3) to establish animal and cellular models of VMC. H&E staining revealed the...
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| Format: | Article |
| Language: | English |
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BMC
2022-01-01
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| Series: | BMC Cardiovascular Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12872-021-02438-z |
| _version_ | 1819261186054553600 |
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| author | Bin Li Xing Xie |
| author_facet | Bin Li Xing Xie |
| author_sort | Bin Li |
| collection | DOAJ |
| description | Abstract Objective To investigate the effect of A20 and how A20 is regulated in viral myocarditis (VMC). Methods BABL/C mice, primary neonatal rat cardiomyocytes and H9c2 cells were infected with Coxsackie virus B3 (CVB3) to establish animal and cellular models of VMC. H&E staining revealed the pathologic condition of myocardium. ELISA measured the serum levels of creatine kinase, creatine kinase isoenzyme and cardiac troponin I. The effects of A20, miR-1a-3p and ADAR1 were investigated using gain and loss of function approaches. ELISA measured the levels of IL-6, IL-18 and TNF-α in serum or cell culture supernatant. TUNEL staining and flow cytometry assessed the apoptosis of myocardium and cardiomyocytes, respectively. RNA-binding protein immunoprecipitation and dual-luciferase reporter assays verified the binding between A20 and miR-1a-3p. Co-immunoprecipitation assay verified the binding between ADAR1 and Dicer. Results A20 was underexpressed and miR-1a-3p was overexpressed in the myocardium of VMC mice as well as in CVB3-infected cardiomyocytes. Overexpression of A20 suppressed cardiomyocyte inflammation and apoptosis in vivo and in vitro. miR-1a-3p promoted CVB3-induced inflammation and apoptosis in cardiomyocytes by binding to A20. The expression of miR-1a-3p was regulated by ADAR1. ADAR1 promoted the slicing of miR-1a-3p precursor by binding to Dicer. Conclusion A20, regulated by ADAR1/miR-1a-3p, suppresses inflammation and cardiomyocyte apoptosis in VMC. |
| first_indexed | 2024-12-23T19:37:47Z |
| format | Article |
| id | doaj.art-945e72aeebc2437a9e82cb3309ddd028 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-12-23T19:37:47Z |
| publishDate | 2022-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-945e72aeebc2437a9e82cb3309ddd0282022-12-21T17:33:45ZengBMCBMC Cardiovascular Disorders1471-22612022-01-0122111210.1186/s12872-021-02438-zA20 (TNFAIP3) alleviates viral myocarditis through ADAR1/miR-1a-3p-dependent regulationBin Li0Xing Xie1Department of Cardiovascular Medicine, Affiliated Hospital of Xiangnan UniversityDepartment of Cardiovascular Medicine, Affiliated Hospital of Xiangnan UniversityAbstract Objective To investigate the effect of A20 and how A20 is regulated in viral myocarditis (VMC). Methods BABL/C mice, primary neonatal rat cardiomyocytes and H9c2 cells were infected with Coxsackie virus B3 (CVB3) to establish animal and cellular models of VMC. H&E staining revealed the pathologic condition of myocardium. ELISA measured the serum levels of creatine kinase, creatine kinase isoenzyme and cardiac troponin I. The effects of A20, miR-1a-3p and ADAR1 were investigated using gain and loss of function approaches. ELISA measured the levels of IL-6, IL-18 and TNF-α in serum or cell culture supernatant. TUNEL staining and flow cytometry assessed the apoptosis of myocardium and cardiomyocytes, respectively. RNA-binding protein immunoprecipitation and dual-luciferase reporter assays verified the binding between A20 and miR-1a-3p. Co-immunoprecipitation assay verified the binding between ADAR1 and Dicer. Results A20 was underexpressed and miR-1a-3p was overexpressed in the myocardium of VMC mice as well as in CVB3-infected cardiomyocytes. Overexpression of A20 suppressed cardiomyocyte inflammation and apoptosis in vivo and in vitro. miR-1a-3p promoted CVB3-induced inflammation and apoptosis in cardiomyocytes by binding to A20. The expression of miR-1a-3p was regulated by ADAR1. ADAR1 promoted the slicing of miR-1a-3p precursor by binding to Dicer. Conclusion A20, regulated by ADAR1/miR-1a-3p, suppresses inflammation and cardiomyocyte apoptosis in VMC.https://doi.org/10.1186/s12872-021-02438-zA20miR-1a-3pADAR1DicerViral myocarditisInflammation |
| spellingShingle | Bin Li Xing Xie A20 (TNFAIP3) alleviates viral myocarditis through ADAR1/miR-1a-3p-dependent regulation BMC Cardiovascular Disorders A20 miR-1a-3p ADAR1 Dicer Viral myocarditis Inflammation |
| title | A20 (TNFAIP3) alleviates viral myocarditis through ADAR1/miR-1a-3p-dependent regulation |
| title_full | A20 (TNFAIP3) alleviates viral myocarditis through ADAR1/miR-1a-3p-dependent regulation |
| title_fullStr | A20 (TNFAIP3) alleviates viral myocarditis through ADAR1/miR-1a-3p-dependent regulation |
| title_full_unstemmed | A20 (TNFAIP3) alleviates viral myocarditis through ADAR1/miR-1a-3p-dependent regulation |
| title_short | A20 (TNFAIP3) alleviates viral myocarditis through ADAR1/miR-1a-3p-dependent regulation |
| title_sort | a20 tnfaip3 alleviates viral myocarditis through adar1 mir 1a 3p dependent regulation |
| topic | A20 miR-1a-3p ADAR1 Dicer Viral myocarditis Inflammation |
| url | https://doi.org/10.1186/s12872-021-02438-z |
| work_keys_str_mv | AT binli a20tnfaip3alleviatesviralmyocarditisthroughadar1mir1a3pdependentregulation AT xingxie a20tnfaip3alleviatesviralmyocarditisthroughadar1mir1a3pdependentregulation |