| 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. |
| Authors | Eva van Rooij, Lillian B Sutherland, Xiaoxia Qi, James A Richardson, Joseph Hill, Eric N Olson
(Affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.)
|
| Journal | Science (New York, N.Y.)
(Science)
Vol. 316
Issue 5824
Pg. 575-9
(Apr 27 2007)
ISSN: 1095-9203 [Electronic] United States |
| PMID | 17379774
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Med13 protein, mouse
- Mediator Complex
- MicroRNAs
- Myosin Heavy Chains
- Transcription Factors
- Triiodothyronine
- Cardiac Myosins
- Ventricular Myosins
|
| Topics |
- Animals
- Cardiac Myosins
(genetics, metabolism)
- Cardiomegaly
(pathology, physiopathology)
- Fibrosis
- Gene Deletion
- Gene Expression Regulation
- Heart
(physiopathology)
- Heart Diseases
(genetics, pathology, physiopathology)
- Hypothyroidism
(physiopathology)
- Introns
- Mediator Complex
- Mice
- Mice, Transgenic
- MicroRNAs
(genetics, physiology)
- Myocardial Contraction
- Myocardium
(metabolism, pathology)
- Myocytes, Cardiac
(pathology)
- Myosin Heavy Chains
(genetics)
- Oligonucleotide Array Sequence Analysis
- Rats
- Signal Transduction
- Stress, Physiological
(physiopathology)
- Transcription Factors
(genetics, metabolism)
- Triiodothyronine
(metabolism)
- Up-Regulation
- Ventricular Myosins
(genetics, metabolism)
|