The transcription factor MEF2C mediates cardiomyocyte hypertrophy induced by IGF-1 signaling
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- 作者：Juan Pablo Muñ ; oz ; Andres Collao ; Mario Chiong ; Carola Maldonado ; Tatiana Adasme ; Loreto Carrasco ; Paula Ocaranza ; Roberto Bravo ; Leticia Gonzalez ; Guillermo Dí ; az-Araya ; Cecilia Hidalgo ; Serg
- 关键词：IGF-1 ; MEF2C ; Hypertrophy ; Heart ; Growth factor ; Cell signaling ; Transcription factor
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2009
- 出版时间：9 October 2009
- 年：2009
- 卷：388
- 期：1
- 页码：155-160
- 全文大小：949 K
文摘
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.