The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling
Myocyte enhancer factor 2C (MEF2C) plays an important role in cardiovascular development and is a key transcription factor for cardiac hypertrophy. Here, we describe MEF2C regulation by insulin-like growth factor-1 (IGF-1) and its role in IGF-1-induced cardiac hypertrophy. We found that IGF-1 addition to cultured rat cardiomyocytes activated MEF2C, as evidenced by its increased nuclear localization and DNA binding activity. IGF-1 stimulated MEF2 dependent-gene transcription in a time-dependent manner, as indicated by increased MEF2 promoter-driven reporter gene activity; IGF-1 also induced p38-MAPK phosphorylation, while an inhibitor of p38-MAPK decreased both effects. Additionally, inhibitors of phosphatidylinositol 3-kinase and calcineurin prevented IGF-1-induced MEF2 transcriptional activity. Via MEF2C-dependent signaling, IGF-1 also stimulated transcription of atrial natriuretic factor and skeletal a-actin but not of fos-lux reporter genes. These novel data suggest that MEF2C activation by IGF-1 mediates the pro-hypertrophic effects of IGF-1 on cardiac gene expression. © 2009 Elsevier Inc. All rights reserved.
|Título según WOS:||The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling|
|Título según SCOPUS:||The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling|
|Título de la Revista:||BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS|
|Editorial:||ACADEMIC PRESS INC ELSEVIER SCIENCE|
|Fecha de publicación:||2009-01-01|
|Página de inicio:||155|