Interferon Regulatory Factor-2 Binding Protein 2 Ameliorates Sepsis-Induced Cardiomyopathy via AMPK-Mediated Anti-Inflammation and Anti-Apoptosis
| Autor: | Qiang Luo, Qingnian Li, Chuntao Wang, Jie Xie, Li He, Da Li, Tianyu Li, Chengla Yi |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male Programmed cell death medicine.medical_treatment Immunology Cardiomyopathy Inflammation Apoptosis AMP-Activated Protein Kinases Sepsis Rats Sprague-Dawley 03 medical and health sciences Mice 0302 clinical medicine Interferon medicine Immunology and Allergy Animals Cells Cultured business.industry AMPK medicine.disease Rats Mice Inbred C57BL 030104 developmental biology Cytokine 030220 oncology & carcinogenesis Cancer research medicine.symptom Interferon Regulatory Factor 2-Binding Protein 2 business Cardiomyopathies medicine.drug Transcription Factors |
| Zdroj: | Inflammation. 43(4) |
| ISSN: | 1573-2576 |
| Popis: | Cardiomyopathy commonly occurs after sepsis and is closely associated with high mortality in clinic. Interferon regulatory factor-2 binding protein 2 (IRF2BP2) has been identified as a negative regulator of inflammation, but its role in septic cardiomyopathy is unknown. The current study aims to illuminate the regulatory function of IRF2BP2 on sepsis-induced cardiomyopathy and to explore the underlying mechanisms. Protein expression of IRF2BP2 in response to sepsis-induced cardiomyopathy was examined in the heart of mice challenged by LPS intraperitoneal injection. AAV9-delivered IRF2BP2 overexpression in the heart was applied to evaluate the regulatory role of IRF2BP2 in sepsis-induced myocardial depression, inflammatory response, and cell death. The molecular mechanisms underlying IRF2BP2-regulated cardiomyopathy were explored using western blot screening assay. Primary cardiomyocytes have been isolated to further confirm the role and mechanism of IRF2BP2 during septic cardiomyopathy. IRF2BP2 expression was dramatically increased in the heart of mice after LPS administration. AAV9-mediated IRF2BP2 overexpression significantly improved sepsis-induced cardiac dysfunction, inhibited inflammatory cell infiltration and cytokine production, and blocked cell death after LPS treatment. Mechanistically, IRF2BP2 activated AMPK signaling in cardiomyocytes, while inhibiting AMPK activation largely reversed IRF2BP2-benefited inflammatory suppression and cell survival. These findings clearly demonstrated that IRF2BP2 is a potent suppressor of sepsis-induced myocardial depression and related heart impairment. Targeting IRF2BP2 represents a promising therapeutic strategy for septic cardiomyopathy. |
| Databáze: | OpenAIRE |
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