MiR-144-3p Enhances Cardiac Fibrosis After Myocardial Infarction by Targeting PTEN

Myocardial infarction (MI) may cause heart failure and seriously harm human health. During the genesis of cardiac fibrosis after MI, the proliferation and migration of cardiac fibroblasts contribute to secretion and maintenance of extracellular matrix (ECM) components. Many miRNAs have been highly i...

Full description

Bibliographic Details
Main Authors: Xiaolong Yuan, Jinchun Pan, Lijuan Wen, Baoyong Gong, Jiaqi Li, Hongbin Gao, Weijiang Tan, Shi Liang, Hao Zhang, Xilong Wang
Format: Article
Language:English
Published: Frontiers Media S.A. 2019-10-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fcell.2019.00249/full
id doaj-ff87c2961bb24b7b9ac2aaaf1ce29f67
record_format Article
collection DOAJ
language English
format Article
sources DOAJ
author Xiaolong Yuan
Xiaolong Yuan
Jinchun Pan
Lijuan Wen
Baoyong Gong
Jiaqi Li
Hongbin Gao
Weijiang Tan
Shi Liang
Hao Zhang
Xilong Wang
spellingShingle Xiaolong Yuan
Xiaolong Yuan
Jinchun Pan
Lijuan Wen
Baoyong Gong
Jiaqi Li
Hongbin Gao
Weijiang Tan
Shi Liang
Hao Zhang
Xilong Wang
MiR-144-3p Enhances Cardiac Fibrosis After Myocardial Infarction by Targeting PTEN
Frontiers in Cell and Developmental Biology
miR-144-3p
PTEN
cardiac fibrosis
myocardial infarction
extracellular matrix
author_facet Xiaolong Yuan
Xiaolong Yuan
Jinchun Pan
Lijuan Wen
Baoyong Gong
Jiaqi Li
Hongbin Gao
Weijiang Tan
Shi Liang
Hao Zhang
Xilong Wang
author_sort Xiaolong Yuan
title MiR-144-3p Enhances Cardiac Fibrosis After Myocardial Infarction by Targeting PTEN
title_short MiR-144-3p Enhances Cardiac Fibrosis After Myocardial Infarction by Targeting PTEN
title_full MiR-144-3p Enhances Cardiac Fibrosis After Myocardial Infarction by Targeting PTEN
title_fullStr MiR-144-3p Enhances Cardiac Fibrosis After Myocardial Infarction by Targeting PTEN
title_full_unstemmed MiR-144-3p Enhances Cardiac Fibrosis After Myocardial Infarction by Targeting PTEN
title_sort mir-144-3p enhances cardiac fibrosis after myocardial infarction by targeting pten
publisher Frontiers Media S.A.
series Frontiers in Cell and Developmental Biology
issn 2296-634X
publishDate 2019-10-01
description Myocardial infarction (MI) may cause heart failure and seriously harm human health. During the genesis of cardiac fibrosis after MI, the proliferation and migration of cardiac fibroblasts contribute to secretion and maintenance of extracellular matrix (ECM) components. Many miRNAs have been highly implicated in the processes of cardiac fibrosis after MI. However, the molecular mechanisms for how miRNAs involve in cardiac fibrosis remain largely unexplored. Based on MI model in miniature pigs, the potential miRNAs involved in MI were identified by using small RNA sequencing. Using human cardiac fibroblasts (HCFs) as a cellular model, EdU, Transwell, and the expression of ECM-related proteins were applied to investigate the cell proliferation, migration and collagen synthesis. In this study, using MI model based on miniature pigs, 84 miRNAs were identified as the differentially expressed miRNAs between MI and control group, and miR-144-3p, one of differentially expressed miRNAs, was identified to be higher expressed in infarct area. The cell proliferation, migration activity, and the mRNA and protein levels of the ECM-related genes were significantly increased by miR-144-3p mimic but significantly decreased by miR-144-3p inhibitor in cardiac fibroblasts. Furthermore, miR-144-3p was observed to repress transcription and translation of PTEN, and interfering with the expression of PTEN up-regulated the mRNAs and proteins levels of α-SMA, Col1A1, and Col3A1, and promoted the proliferation and migration of cardiac fibroblasts, which was in line with that of miR-144-3p mimics, but this observation could be reversed by miR-144-3p inhibitor. Collectively, miR-144-3p promotes cell proliferation, migration, and collagen production by targeting PTEN in cardiac fibroblasts, suggesting that miR-144-3p-mediated-PTEN regulation might be a novel therapeutic target for cardiac fibrosis after MI.
topic miR-144-3p
PTEN
cardiac fibrosis
myocardial infarction
extracellular matrix
url https://www.frontiersin.org/article/10.3389/fcell.2019.00249/full
work_keys_str_mv AT xiaolongyuan mir1443penhancescardiacfibrosisaftermyocardialinfarctionbytargetingpten
AT xiaolongyuan mir1443penhancescardiacfibrosisaftermyocardialinfarctionbytargetingpten
AT jinchunpan mir1443penhancescardiacfibrosisaftermyocardialinfarctionbytargetingpten
AT lijuanwen mir1443penhancescardiacfibrosisaftermyocardialinfarctionbytargetingpten
AT baoyonggong mir1443penhancescardiacfibrosisaftermyocardialinfarctionbytargetingpten
AT jiaqili mir1443penhancescardiacfibrosisaftermyocardialinfarctionbytargetingpten
AT hongbingao mir1443penhancescardiacfibrosisaftermyocardialinfarctionbytargetingpten
AT weijiangtan mir1443penhancescardiacfibrosisaftermyocardialinfarctionbytargetingpten
AT shiliang mir1443penhancescardiacfibrosisaftermyocardialinfarctionbytargetingpten
AT haozhang mir1443penhancescardiacfibrosisaftermyocardialinfarctionbytargetingpten
AT xilongwang mir1443penhancescardiacfibrosisaftermyocardialinfarctionbytargetingpten
_version_ 1724732161564606464
spelling doaj-ff87c2961bb24b7b9ac2aaaf1ce29f672020-11-25T02:51:58ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2019-10-01710.3389/fcell.2019.00249485668MiR-144-3p Enhances Cardiac Fibrosis After Myocardial Infarction by Targeting PTENXiaolong Yuan0Xiaolong Yuan1Jinchun Pan2Lijuan Wen3Baoyong Gong4Jiaqi Li5Hongbin Gao6Weijiang Tan7Shi Liang8Hao Zhang9Xilong Wang10Guangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, ChinaNational Engineering Research Center for Swine Breeding Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, ChinaNational Engineering Research Center for Swine Breeding Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, ChinaNational Engineering Research Center for Swine Breeding Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, ChinaNational Engineering Research Center for Swine Breeding Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, ChinaMyocardial infarction (MI) may cause heart failure and seriously harm human health. During the genesis of cardiac fibrosis after MI, the proliferation and migration of cardiac fibroblasts contribute to secretion and maintenance of extracellular matrix (ECM) components. Many miRNAs have been highly implicated in the processes of cardiac fibrosis after MI. However, the molecular mechanisms for how miRNAs involve in cardiac fibrosis remain largely unexplored. Based on MI model in miniature pigs, the potential miRNAs involved in MI were identified by using small RNA sequencing. Using human cardiac fibroblasts (HCFs) as a cellular model, EdU, Transwell, and the expression of ECM-related proteins were applied to investigate the cell proliferation, migration and collagen synthesis. In this study, using MI model based on miniature pigs, 84 miRNAs were identified as the differentially expressed miRNAs between MI and control group, and miR-144-3p, one of differentially expressed miRNAs, was identified to be higher expressed in infarct area. The cell proliferation, migration activity, and the mRNA and protein levels of the ECM-related genes were significantly increased by miR-144-3p mimic but significantly decreased by miR-144-3p inhibitor in cardiac fibroblasts. Furthermore, miR-144-3p was observed to repress transcription and translation of PTEN, and interfering with the expression of PTEN up-regulated the mRNAs and proteins levels of α-SMA, Col1A1, and Col3A1, and promoted the proliferation and migration of cardiac fibroblasts, which was in line with that of miR-144-3p mimics, but this observation could be reversed by miR-144-3p inhibitor. Collectively, miR-144-3p promotes cell proliferation, migration, and collagen production by targeting PTEN in cardiac fibroblasts, suggesting that miR-144-3p-mediated-PTEN regulation might be a novel therapeutic target for cardiac fibrosis after MI.https://www.frontiersin.org/article/10.3389/fcell.2019.00249/fullmiR-144-3pPTENcardiac fibrosismyocardial infarctionextracellular matrix