Pro-fibrotic and apoptotic activities of circARAP1 in myocardial ischemia–reperfusion injury
Abstract Reperfusion modality can cause damage to cardiomyocytes, known as myocardial ischemia–reperfusion injury (MI/RI). Circular RNAs (circRNAs) are fundamental regulators associated with many cardiac diseases, including MI/RI. However, their functional impact on cardiomyocyte fibrosis and apopto...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-023-01001-0 |
| _version_ | 1797865230325252096 |
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| author | Xi Li Lei Guo Jingjing Wang Xing Yang |
| author_facet | Xi Li Lei Guo Jingjing Wang Xing Yang |
| author_sort | Xi Li |
| collection | DOAJ |
| description | Abstract Reperfusion modality can cause damage to cardiomyocytes, known as myocardial ischemia–reperfusion injury (MI/RI). Circular RNAs (circRNAs) are fundamental regulators associated with many cardiac diseases, including MI/RI. However, their functional impact on cardiomyocyte fibrosis and apoptosis remains elusive. Therefore, this study aimed to explore possible molecular mechanisms of circARPA1 in animal models and in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. GEO dataset analysis showed that has_circ_0023461 (circARPA1) was differentially expressed in myocardial infarction samples. Real-time quantitative PCR further supported that circARPA1 was expressed at high levels in animal models and in H/R-triggered cardiomyocytes. Then, loss-of-function assays were performed to show that circARAP1 suppression effectively ameliorated cardiomyocyte fibrosis and apoptosis in MI/RI mice. Mechanistic experiments showed that miR-379-5p, KLF9 and Wnt signaling pathways were associated with circARPA1. circARPA1 can sponge miR-379-5p to regulate KLF9 expression, thereby activating the wnt/β-catenin pathway. Finally, gain-of-function assays revealed that circARAP1 aggravated MI/RI in mice and H/R-induced cardiomyocyte injury by regulating the miR-379-5p/KLF9 axis to activate Wnt/β-catenin signaling. |
| first_indexed | 2024-04-09T23:05:50Z |
| format | Article |
| id | doaj.art-f5909a7abe5c49b19f6fbe8298c0834e |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-04-09T23:05:50Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-f5909a7abe5c49b19f6fbe8298c0834e2023-03-22T10:46:11ZengBMCEuropean Journal of Medical Research2047-783X2023-02-0128111310.1186/s40001-023-01001-0Pro-fibrotic and apoptotic activities of circARAP1 in myocardial ischemia–reperfusion injuryXi Li0Lei Guo1Jingjing Wang2Xing Yang3Department of Cardiology, General Hospital of Ningxia Medical UniversityDepartment of Cardiology, Yan’an University Xianyang HospitalDepartment of Cardiology, General Hospital of Ningxia Medical UniversityDepartment of Cardiology, Yan’an University Xianyang HospitalAbstract Reperfusion modality can cause damage to cardiomyocytes, known as myocardial ischemia–reperfusion injury (MI/RI). Circular RNAs (circRNAs) are fundamental regulators associated with many cardiac diseases, including MI/RI. However, their functional impact on cardiomyocyte fibrosis and apoptosis remains elusive. Therefore, this study aimed to explore possible molecular mechanisms of circARPA1 in animal models and in hypoxia/reoxygenation (H/R)-treated cardiomyocytes. GEO dataset analysis showed that has_circ_0023461 (circARPA1) was differentially expressed in myocardial infarction samples. Real-time quantitative PCR further supported that circARPA1 was expressed at high levels in animal models and in H/R-triggered cardiomyocytes. Then, loss-of-function assays were performed to show that circARAP1 suppression effectively ameliorated cardiomyocyte fibrosis and apoptosis in MI/RI mice. Mechanistic experiments showed that miR-379-5p, KLF9 and Wnt signaling pathways were associated with circARPA1. circARPA1 can sponge miR-379-5p to regulate KLF9 expression, thereby activating the wnt/β-catenin pathway. Finally, gain-of-function assays revealed that circARAP1 aggravated MI/RI in mice and H/R-induced cardiomyocyte injury by regulating the miR-379-5p/KLF9 axis to activate Wnt/β-catenin signaling.https://doi.org/10.1186/s40001-023-01001-0Myocardial ischemia–reperfusion injurycircARPA1miR-379-5pKLF9Wnt pathway |
| spellingShingle | Xi Li Lei Guo Jingjing Wang Xing Yang Pro-fibrotic and apoptotic activities of circARAP1 in myocardial ischemia–reperfusion injury European Journal of Medical Research Myocardial ischemia–reperfusion injury circARPA1 miR-379-5p KLF9 Wnt pathway |
| title | Pro-fibrotic and apoptotic activities of circARAP1 in myocardial ischemia–reperfusion injury |
| title_full | Pro-fibrotic and apoptotic activities of circARAP1 in myocardial ischemia–reperfusion injury |
| title_fullStr | Pro-fibrotic and apoptotic activities of circARAP1 in myocardial ischemia–reperfusion injury |
| title_full_unstemmed | Pro-fibrotic and apoptotic activities of circARAP1 in myocardial ischemia–reperfusion injury |
| title_short | Pro-fibrotic and apoptotic activities of circARAP1 in myocardial ischemia–reperfusion injury |
| title_sort | pro fibrotic and apoptotic activities of circarap1 in myocardial ischemia reperfusion injury |
| topic | Myocardial ischemia–reperfusion injury circARPA1 miR-379-5p KLF9 Wnt pathway |
| url | https://doi.org/10.1186/s40001-023-01001-0 |
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