Control of stress-dependent cardiac growth and gene expression by a microRNA.
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.
van Rooij
Eva
E
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Sutherland
Lillian B
LB
Qi
Xiaoxia
X
Richardson
James A
JA
Hill
Joseph
J
Olson
Eric N
EN
D000818:Animals; D024722:Cardiac Myosins / Q000235:genetics / Q000378:metabolism; D006332:Cardiomegaly / Q000473:pathology / Q000503:physiopathology; D005355:Fibrosis; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology; D006331:Heart Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D007037:Hypothyroidism / Q000503:physiopathology; D007438:Introns; D056892:Mediator Complex; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D015398:Signal Transduction; D013312:Stress, Physiological / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism; D015854:Up-Regulation; D024723:Ventricular Myosins / Q000235:genetics* / Q000378:metabolism
C519602:Med13 protein, mouse; D056892:Mediator Complex; D035683:MicroRNAs; D014157:Transcription Factors; D014284:Triiodothyronine; D024722:Cardiac Myosins; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains