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

• Published in: Biochemical and biophysical research communications Vol. 388; no. 1; pp. 155 - 160
• Main Authors: Muñoz, Juan Pablo, Collao, Andres, Chiong, Mario, Maldonado, Carola, Adasme, Tatiana, Carrasco, Loreto, Ocaranza, Paula, Bravo, Roberto, Gonzalez, Leticia, Díaz-Araya, Guillermo, Hidalgo, Cecilia, Lavandero, Sergio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09-10-2009
• Subjects: 60 APPLIED LIFE SCIENCES; ACTIN; Animals; Calcineurin - metabolism; Calcineurin Inhibitors; Cardiomegaly - genetics; Cardiomegaly - metabolism; Cardiomegaly - pathology; Cell Nucleus - metabolism; Cell signaling; Cells, Cultured; DNA; Gene Expression Regulation; GENE REGULATION; GENES; Growth factor; GROWTH FACTORS; HEART; HYPERTROPHY; IGF-1; INSULIN; Insulin-Like Growth Factor I - metabolism; MEF2 Transcription Factors; MEF2C; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Myogenic Regulatory Factors - metabolism; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - metabolism; PHOSPHORYLATION; Promoter Regions, Genetic; PROMOTERS; RATS; Signal Transduction; TIME DEPENDENCE; TRANSCRIPTION; Transcription factor; TRANSCRIPTION FACTORS; Transcription, Genetic; Heart; MEF2C; IGF-1; Transcription factor; Cell signaling; Hypertrophy; Growth factor
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2009.07.147

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 α-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.