circRNA Hipk3 Induces Cardiac Regeneration after Myocardial Infarction in Mice by Binding to Notch1 and miR-133a
The synergism between cardiomyogenesis and angiogenesis is essential for cardiac regeneration. Circular RNAs (circRNAs) play pivotal roles in cell growth and angiogenesis, but their functions in cardiac regeneration are not yet known. In this study, we investigated the role and underlying mechanisms...
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Format: | Article |
Language: | English |
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Elsevier
2020-09-01
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Series: | Molecular Therapy: Nucleic Acids |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120301852 |
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doaj-535a932e8d8747ddb053b38b92d3dc52 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiaoyun Si Hao Zheng Guoquan Wei Mengsha Li Wei Li Houmei Wang Haijun Guo Jie Sun Chuling Li Shenrong Zhong Wangjun Liao Yulin Liao Senlin Huang Jianping Bin |
spellingShingle |
Xiaoyun Si Hao Zheng Guoquan Wei Mengsha Li Wei Li Houmei Wang Haijun Guo Jie Sun Chuling Li Shenrong Zhong Wangjun Liao Yulin Liao Senlin Huang Jianping Bin circRNA Hipk3 Induces Cardiac Regeneration after Myocardial Infarction in Mice by Binding to Notch1 and miR-133a Molecular Therapy: Nucleic Acids circRNA angiogenesis cardiac regeneration |
author_facet |
Xiaoyun Si Hao Zheng Guoquan Wei Mengsha Li Wei Li Houmei Wang Haijun Guo Jie Sun Chuling Li Shenrong Zhong Wangjun Liao Yulin Liao Senlin Huang Jianping Bin |
author_sort |
Xiaoyun Si |
title |
circRNA Hipk3 Induces Cardiac Regeneration after Myocardial Infarction in Mice by Binding to Notch1 and miR-133a |
title_short |
circRNA Hipk3 Induces Cardiac Regeneration after Myocardial Infarction in Mice by Binding to Notch1 and miR-133a |
title_full |
circRNA Hipk3 Induces Cardiac Regeneration after Myocardial Infarction in Mice by Binding to Notch1 and miR-133a |
title_fullStr |
circRNA Hipk3 Induces Cardiac Regeneration after Myocardial Infarction in Mice by Binding to Notch1 and miR-133a |
title_full_unstemmed |
circRNA Hipk3 Induces Cardiac Regeneration after Myocardial Infarction in Mice by Binding to Notch1 and miR-133a |
title_sort |
circrna hipk3 induces cardiac regeneration after myocardial infarction in mice by binding to notch1 and mir-133a |
publisher |
Elsevier |
series |
Molecular Therapy: Nucleic Acids |
issn |
2162-2531 |
publishDate |
2020-09-01 |
description |
The synergism between cardiomyogenesis and angiogenesis is essential for cardiac regeneration. Circular RNAs (circRNAs) play pivotal roles in cell growth and angiogenesis, but their functions in cardiac regeneration are not yet known. In this study, we investigated the role and underlying mechanisms of circRNA Hipk3 (circHipk3) in both cardiomyogenesis and angiogenesis during cardiac regeneration. We found that circHipk3 was overexpressed in the fetal or neonatal heart of mice. The transcription factor Gata4 bound to the circHipk3 promoter and increased circHipk3 expression. Cardiomyocyte (CM) proliferation in vitro and in vivo was inhibited by circHipk3 knockdown and increased by circHipk3 overexpression. Moreover, circHipk3 overexpression promoted coronary vessel endothelial cell proliferation, migration, and tube-forming capacity and subsequent angiogenesis. More importantly, circHipk3 overexpression attenuated cardiac dysfunction and decreased fibrotic area after myocardial infarction (MI). Mechanistically, circHipk3 promoted CM proliferation by increasing Notch1 intracellular domain (N1ICD) acetylation, thereby increasing N1ICD stability and preventing its degradation. In addition, circHipk3 acted as a sponge for microRNA (miR)-133a to promote connective tissue growth factor (CTGF) expression, which activated endothelial cells. Our findings suggested that circHipk3 might be a novel therapeutic target for preventing heart failure post-MI. |
topic |
circRNA angiogenesis cardiac regeneration |
url |
http://www.sciencedirect.com/science/article/pii/S2162253120301852 |
work_keys_str_mv |
AT xiaoyunsi circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT haozheng circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT guoquanwei circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT mengshali circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT weili circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT houmeiwang circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT haijunguo circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT jiesun circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT chulingli circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT shenrongzhong circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT wangjunliao circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT yulinliao circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT senlinhuang circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a AT jianpingbin circrnahipk3inducescardiacregenerationaftermyocardialinfarctioninmicebybindingtonotch1andmir133a |
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1724586325749792768 |
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doaj-535a932e8d8747ddb053b38b92d3dc522020-11-25T03:27:56ZengElsevierMolecular Therapy: Nucleic Acids2162-25312020-09-0121636655circRNA Hipk3 Induces Cardiac Regeneration after Myocardial Infarction in Mice by Binding to Notch1 and miR-133aXiaoyun Si0Hao Zheng1Guoquan Wei2Mengsha Li3Wei Li4Houmei Wang5Haijun Guo6Jie Sun7Chuling Li8Shenrong Zhong9Wangjun Liao10Yulin Liao11Senlin Huang12Jianping Bin13Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Department of Cardiology, Guizhou Medical University, Affiliated Hospital, Guizhou 550004, ChinaDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Cardiology, Guizhou Medical University, Affiliated Hospital, Guizhou 550004, ChinaDepartment of Obstetrics and Gynecology, Guizhou Medical University, Affiliated Hospital, Guizhou 550004, ChinaDepartment of Cardiology, Guizhou Medical University, Affiliated Hospital, Guizhou 550004, ChinaDepartment of Cardiology, Zhongshan People’s Hospital, Zhongshan 528403, ChinaDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, ChinaDepartment of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Corresponding author: Senlin Huang, MD, Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, China.Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Corresponding author: Jianping Bin, MD, PhD, Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, China.The synergism between cardiomyogenesis and angiogenesis is essential for cardiac regeneration. Circular RNAs (circRNAs) play pivotal roles in cell growth and angiogenesis, but their functions in cardiac regeneration are not yet known. In this study, we investigated the role and underlying mechanisms of circRNA Hipk3 (circHipk3) in both cardiomyogenesis and angiogenesis during cardiac regeneration. We found that circHipk3 was overexpressed in the fetal or neonatal heart of mice. The transcription factor Gata4 bound to the circHipk3 promoter and increased circHipk3 expression. Cardiomyocyte (CM) proliferation in vitro and in vivo was inhibited by circHipk3 knockdown and increased by circHipk3 overexpression. Moreover, circHipk3 overexpression promoted coronary vessel endothelial cell proliferation, migration, and tube-forming capacity and subsequent angiogenesis. More importantly, circHipk3 overexpression attenuated cardiac dysfunction and decreased fibrotic area after myocardial infarction (MI). Mechanistically, circHipk3 promoted CM proliferation by increasing Notch1 intracellular domain (N1ICD) acetylation, thereby increasing N1ICD stability and preventing its degradation. In addition, circHipk3 acted as a sponge for microRNA (miR)-133a to promote connective tissue growth factor (CTGF) expression, which activated endothelial cells. Our findings suggested that circHipk3 might be a novel therapeutic target for preventing heart failure post-MI.http://www.sciencedirect.com/science/article/pii/S2162253120301852circRNAangiogenesiscardiac regeneration |