Abstract
The heart responds to diverse forms of stress by hypertrophic growth accompanied by fibrosis and eventual diminution of contractility, which results from down-regulation of alpha-myosin heavy chain (alphaMHC) and up-regulation of betaMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the alphaMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of betaMHC in response to stress and hypothyroidism. Thus, the alphaMHC gene, in addition to encoding a major cardiac contractile protein, regulates cardiac growth and gene expression in response to stress and hormonal signaling through miR-208.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cardiac Myosins / genetics
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Cardiac Myosins / metabolism
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Cardiomegaly / pathology
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Cardiomegaly / physiopathology
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Fibrosis
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Gene Deletion
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Gene Expression Regulation*
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Heart / physiopathology
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Heart Diseases / genetics*
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Heart Diseases / pathology
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Heart Diseases / physiopathology
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Hypothyroidism / physiopathology
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Introns
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Mediator Complex
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Mice
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Mice, Transgenic
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MicroRNAs / genetics
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MicroRNAs / physiology*
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Myocardial Contraction
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Myocardium / metabolism*
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Myocardium / pathology*
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Myocytes, Cardiac / pathology
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Myosin Heavy Chains / genetics*
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Oligonucleotide Array Sequence Analysis
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Rats
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Signal Transduction
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Stress, Physiological / physiopathology
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Triiodothyronine / metabolism
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Up-Regulation
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Ventricular Myosins / genetics*
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Ventricular Myosins / metabolism
Substances
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Med13 protein, mouse
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Mediator Complex
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MicroRNAs
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Transcription Factors
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Triiodothyronine
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Cardiac Myosins
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Ventricular Myosins
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Myosin Heavy Chains