MiR-155 Knockout in Fibroblasts Improves Cardiac Remodeling by Targeting Tumor Protein p53-Inducible Nuclear Protein 1

Cardiac remodeling caused by acute myocardial infarction (AMI) represents a major challenge for heart failure research. MiR-155 has been identified as a key mediator of cardiac inflammation and hypertrophy. In this study, we investigate the role of miR-155 in cardiac remodeling induced by AMI. We de...

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Bibliographic Details
Published in:Journal of cardiovascular pharmacology and therapeutics 2016-07, Vol.21 (4), p.423-435
Main Authors: He, Wangwei, Huang, He, Xie, Qiang, Wang, Zhiqiang, Fan, Yang, Kong, Bin, Huang, Dan, Xiao, Yali
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation
Cell Proliferation
Cells, Cultured
Collagen - metabolism
Disease Models, Animal
Fibroblasts - metabolism
Fibroblasts - pathology
Gene Expression Regulation
Genotype
Male
Mice, Inbred C57BL
Mice, Knockout
MicroRNAs - genetics
MicroRNAs - metabolism
Myocardial Infarction - genetics
Myocardial Infarction - metabolism
Myocardial Infarction - pathology
Myocardial Infarction - physiopathology
Myocardium - metabolism
Myocardium - pathology
Myofibroblasts - metabolism
Myofibroblasts - pathology
Nuclear Proteins - genetics
Nuclear Proteins - metabolism
Phenotype
RNA Interference
Signal Transduction
Time Factors
Transfection
Ventricular Function, Left
Ventricular Remodeling
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Summary:Cardiac remodeling caused by acute myocardial infarction (AMI) represents a major challenge for heart failure research. MiR-155 has been identified as a key mediator of cardiac inflammation and hypertrophy. In this study, we investigate the role of miR-155 in cardiac remodeling induced by AMI. We demonstrate that miR-155 expressed in cardiac fibroblasts is a potent contributor to cardiac remodeling. We reveal that in vivo, miR-155 knockout improves left ventricular function, reduces infarct size, and attenuates collagen deposition, whereas overexpression of miR-155 produces the opposite effects. MiR-155 knockout also inhibits cardiac fibroblast proliferation and differentiation into myofibroblasts. In addition, downregulation of tumor protein p53-inducible nuclear protein 1 (TP53INP1) by small interfering RNA reverses the effects of miR-155 knockout on cardiac fibroblasts. Our data reveal that knockout of miR-155 in cardiac fibroblasts improves cardiac remodeling by targeting TP53INP1, which may be a novel treatment strategy for cardiac remodeling.
ISSN:1074-2484
1940-4034
DOI:10.1177/1074248415616188