The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling

Munoz, JP; Collao, A; Chiong M.; Maldonado, C; Adasme, T.; CARRASCO L.; Ocaranza, P; Bravo, R.; Gonzalez L.; Diaz-Araya, G; Hidalgo C.; Lavandero S.

Abstract

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.

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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
Volumen: 388
Asunto: 1
Editorial: ACADEMIC PRESS INC ELSEVIER SCIENCE
Fecha de publicación: 2009-01-01
Página de inicio: 155
Página final: 160
Idioma: English
DOI/URL:

10.1016/j.bbrc.2009.07.147

Identificador: 10.1016/j.bbrc.2009.07.147
Notas: ISI, SCOPUS