miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN
Previously, we found that the miR-217 expression level was increased in hearts from chronic heart failure (CHF) patients by using miRNA profile analysis. This study aimed to explore the role of miR-217 in cardiac dysfunction. Heart tissue samples from CHF patients were used to detect miR-217 express...
Main Authors: | , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Elsevier
2018-09-01
|
Series: | Molecular Therapy: Nucleic Acids |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253118301100 |
id |
doaj-2b3d19174072465b998ef32552d4bf1d |
---|---|
record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiang Nie Jiahui Fan Huaping Li Zhongwei Yin Yanru Zhao Beibei Dai Nianguo Dong Chen Chen Dao Wen Wang |
spellingShingle |
Xiang Nie Jiahui Fan Huaping Li Zhongwei Yin Yanru Zhao Beibei Dai Nianguo Dong Chen Chen Dao Wen Wang miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN Molecular Therapy: Nucleic Acids |
author_facet |
Xiang Nie Jiahui Fan Huaping Li Zhongwei Yin Yanru Zhao Beibei Dai Nianguo Dong Chen Chen Dao Wen Wang |
author_sort |
Xiang Nie |
title |
miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN |
title_short |
miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN |
title_full |
miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN |
title_fullStr |
miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN |
title_full_unstemmed |
miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTEN |
title_sort |
mir-217 promotes cardiac hypertrophy and dysfunction by targeting pten |
publisher |
Elsevier |
series |
Molecular Therapy: Nucleic Acids |
issn |
2162-2531 |
publishDate |
2018-09-01 |
description |
Previously, we found that the miR-217 expression level was increased in hearts from chronic heart failure (CHF) patients by using miRNA profile analysis. This study aimed to explore the role of miR-217 in cardiac dysfunction. Heart tissue samples from CHF patients were used to detect miR-217 expression levels. A type 9 recombinant adeno-associated virus (rAAV9) was employed to manipulate miR-217 expression in mice with thoracic aortic constriction (TAC)-induced cardiac dysfunction. Cardiac structure and function were measured by echocardiography and invasive pressure-volume analysis. The expression levels of miR-217 were increased in hearts from both CHF patients and TAC mice. Overexpression of miR-217 in vivo aggravated pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction, whereas miR-217-TUD-mediated downregulation of miR-217 reversed these effects. PTEN was predicted and validated as a direct target of miR-217, and re-expression of PTEN attenuated miR-217-mediated cardiac hypertrophy and cardiac dysfunction. Importantly, cardiomyocyte-derived miR-217-containing exosomes enhanced proliferation of fibroblasts in vitro. All of these findings show that miR-217 participates in cardiac hypertrophy and cardiac fibrosis processes through regulating PTEN, which suggests a promising therapeutic target for CHF. Keywords: miR-217, PTEN, cardiac hypertrophy, exosome |
url |
http://www.sciencedirect.com/science/article/pii/S2162253118301100 |
work_keys_str_mv |
AT xiangnie mir217promotescardiachypertrophyanddysfunctionbytargetingpten AT jiahuifan mir217promotescardiachypertrophyanddysfunctionbytargetingpten AT huapingli mir217promotescardiachypertrophyanddysfunctionbytargetingpten AT zhongweiyin mir217promotescardiachypertrophyanddysfunctionbytargetingpten AT yanruzhao mir217promotescardiachypertrophyanddysfunctionbytargetingpten AT beibeidai mir217promotescardiachypertrophyanddysfunctionbytargetingpten AT nianguodong mir217promotescardiachypertrophyanddysfunctionbytargetingpten AT chenchen mir217promotescardiachypertrophyanddysfunctionbytargetingpten AT daowenwang mir217promotescardiachypertrophyanddysfunctionbytargetingpten |
_version_ |
1725820012224053248 |
spelling |
doaj-2b3d19174072465b998ef32552d4bf1d2020-11-24T22:07:31ZengElsevierMolecular Therapy: Nucleic Acids2162-25312018-09-0112254266miR-217 Promotes Cardiac Hypertrophy and Dysfunction by Targeting PTENXiang Nie0Jiahui Fan1Huaping Li2Zhongwei Yin3Yanru Zhao4Beibei Dai5Nianguo Dong6Chen Chen7Dao Wen Wang8Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Wuhan 430030, ChinaDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Wuhan 430030, ChinaDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Wuhan 430030, ChinaDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Wuhan 430030, ChinaDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Wuhan 430030, ChinaDivision of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Corresponding author: Nianguo Dong, Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Wuhan 430030, China; Corresponding author: Chen Chen, Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Huazhong University of Science and Technology, Wuhan 430030, ChinaPreviously, we found that the miR-217 expression level was increased in hearts from chronic heart failure (CHF) patients by using miRNA profile analysis. This study aimed to explore the role of miR-217 in cardiac dysfunction. Heart tissue samples from CHF patients were used to detect miR-217 expression levels. A type 9 recombinant adeno-associated virus (rAAV9) was employed to manipulate miR-217 expression in mice with thoracic aortic constriction (TAC)-induced cardiac dysfunction. Cardiac structure and function were measured by echocardiography and invasive pressure-volume analysis. The expression levels of miR-217 were increased in hearts from both CHF patients and TAC mice. Overexpression of miR-217 in vivo aggravated pressure overload-induced cardiac hypertrophy, fibrosis, and cardiac dysfunction, whereas miR-217-TUD-mediated downregulation of miR-217 reversed these effects. PTEN was predicted and validated as a direct target of miR-217, and re-expression of PTEN attenuated miR-217-mediated cardiac hypertrophy and cardiac dysfunction. Importantly, cardiomyocyte-derived miR-217-containing exosomes enhanced proliferation of fibroblasts in vitro. All of these findings show that miR-217 participates in cardiac hypertrophy and cardiac fibrosis processes through regulating PTEN, which suggests a promising therapeutic target for CHF. Keywords: miR-217, PTEN, cardiac hypertrophy, exosomehttp://www.sciencedirect.com/science/article/pii/S2162253118301100 |