Abstract
Vascular endothelial growth factor (VEGF) is an essential cytokine that has functions in the formation of new blood vessels and regression of cardiac hypertrophy. VEGF/VEGF-receptor-1 (VEGFR1) signaling plays a key role in the regression of cardiac hypertrophy, whereas VEGF/VEGFR2 signaling leads to cardiac hypertrophy. In this study, we identified the prohypertrophic role of miR-374 using neonatal rat ventricular myocytes (NRVMs). Our results showed that overexpression of miR-374 activated G protein-coupled receptor-mediated prohypertrophic pathways by the inhibition of VEGFR1-dependent regression pathways. Luciferase assays revealed that miR-374 could directly target the 3'-untranslated regions of VEGFR1 and cGMP-dependent protein kinase-1. Collectively, these findings demonstrated that miR-374 was a novel pro-hypertrophic microRNA functioning to suppress the VEGFR1-mediated regression pathway. [BMB Reports 2017; 50(4): 208-213].
MeSH terms
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3' Untranslated Regions
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Animals
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Antagomirs / metabolism
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Base Sequence
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Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
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Cardiomegaly / genetics
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Cardiomegaly / metabolism
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Cardiomegaly / pathology
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Cells, Cultured
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Cyclic GMP-Dependent Protein Kinase Type I / antagonists & inhibitors
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Cyclic GMP-Dependent Protein Kinase Type I / genetics
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Cyclic GMP-Dependent Protein Kinase Type I / metabolism
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Genes, Reporter
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MEF2 Transcription Factors / metabolism
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MicroRNAs / antagonists & inhibitors
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MicroRNAs / genetics
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MicroRNAs / metabolism*
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Myocytes, Cardiac / cytology
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Myocytes, Cardiac / metabolism
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NFATC Transcription Factors / metabolism
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RNA Interference
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RNA, Small Interfering / metabolism
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Rats
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Rats, Sprague-Dawley
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Sequence Alignment
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Signal Transduction*
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Vascular Endothelial Growth Factor Receptor-1 / antagonists & inhibitors
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Vascular Endothelial Growth Factor Receptor-1 / genetics
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Vascular Endothelial Growth Factor Receptor-1 / metabolism*
Substances
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3' Untranslated Regions
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Antagomirs
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MEF2 Transcription Factors
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MicroRNAs
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NFATC Transcription Factors
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RNA, Small Interfering
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Vascular Endothelial Growth Factor Receptor-1
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Cyclic GMP-Dependent Protein Kinase Type I
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Calcium-Calmodulin-Dependent Protein Kinase Type 2