Rationale: Failing cardiomyocytes exhibit decreased efficiency of excitation-contraction (E-C) coupling. The downregulation of junctophilin-2 (JP2), a protein anchoring the sarcoplasmic reticulum to T-tubules, has been identified as a major mechanism underlying the defective E-C coupling. However, the regulatory mechanism of JP2 remains unknown. Objective: To determine whether microRNAs regulate JP2 expression. Methods and Results: Bioinformatic analysis predicted 2 potential binding sites of miR-24 in the 3'-untranslated regions of JP2 mRNA. Luciferase assays confirmed that miR-24 suppressed JP2 expression by binding to either of these sites. In the aortic stenosis model, miR-24 was upregulated in failing cardiomyocytes. Adenovirus-directed overexpression of miR-24 in cardiomyocytes decreased JP2 expression and reduced Ca2+ transient amplitude and E-C coupling gain. Conclusions: MiR-24-mediated suppression of JP2 expression provides a novel molecular mechanism for E-C coupling regulation in heart cells and suggests a new target against heart failure. (Circ Res. 2012;111:837-841.)
基金：
973 Program of ChinaNational Basic Research Program of China [2011CB809101, 2011CBA01101]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [30800475, 81070196, 81030001, 30730013]; 863 Program of China [2011AA020108]; Program for New Century Excellent Talents in UniversityProgram for New Century Excellent Talents in University (NCET); Beijing Talents Foundation; National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01TW007269]
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外文
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中科院(CAS)分区：
出版当年[2011]版：
大类|1 区医学
小类|1 区心脏和心血管系统1 区血液学1 区外周血管病
最新[2023]版：
大类|1 区医学
小类|1 区心脏和心血管系统1 区血液学1 区外周血管病
JCR分区：
出版当年[2010]版：
Q1HEMATOLOGYQ1PERIPHERAL VASCULAR DISEASEQ1CARDIAC & CARDIOVASCULAR SYSTEMS
医学