Control of stress-dependent cardiac growth and gene expression by a microRNA

E Van Rooij, LB Sutherland, X Qi, JA Richardson, J Hill… - science, 2007 - science.org
E Van Rooij, LB Sutherland, X Qi, JA Richardson, J Hill, EN Olson
science, 2007science.org
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 α–
myosin heavy chain (αMHC) and up-regulation of βMHC, the primary contractile proteins of
the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the
α MHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of β MHC in
response to stress and hypothyroidism. Thus, the α MHC gene, in addition to encoding a …
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 α–myosin heavy chain (αMHC) and up-regulation of βMHC, the primary contractile proteins of the heart. We found that a cardiac-specific microRNA (miR-208) encoded by an intron of the αMHC gene is required for cardiomyocyte hypertrophy, fibrosis, and expression of βMHC in response to stress and hypothyroidism. Thus, the αMHC 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.
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