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(Circulation Research. 2001;88:1231.)
© 2001 American Heart Association, Inc.

Molecular Medicine

Developing a Strategy to Define the Effects of Insulin-Like Growth Factor-1 on Gene Expression Profile in Cardiomyocytes

Tsun-jui Liu, Hui-chin Lai, Weihua Wu, Steven Chinn, Ping H. Wang

From the Departments of Medicine and Biological Chemistry (T.L., H.L., W.W., S.C., P.H.W.), Division of Endocrinology, Diabetes, and Metabolism, University of California, Irvine, and the Veterans General Hospital-Taichung and National Yang-Ming University (T.L., H.L.), Taipei, Taiwan.

Correspondence to Ping H. Wang, MD, Department of Medicine, Med Sci I, Room C240, University of California, Irvine, CA 92697. E-mail phwang{at}uci.edu

Abstract

Abstract—Insulin-like growth factor (IGF)-1 activates intracellular signaling pathways and regulates myocardial structure and function. This study used DNA microarray to define the effects of IGF-1 on gene expression in cardiomyocytes. Despite DNA microarray becoming a popular tool for profiling gene expression, the specificity of DNA microarray results is rarely addressed. Our data showed that the specificity of a DNA microarray study can be increased by repetitive experiments and by excluding minimally expressed genes. In this study, the false-positive rates were reduced to <0.2%. Future DNA microarray studies should incorporate a proper strategy to minimize false-positive results. IGF-1 modulates the expression of genes in 17 functional categories, but most genes clustered around the regulation of intracellular signaling, cell cycle, transcription/translation, cellular respiration and mitochondrial function, cell survival, ion channels and calcium signaling, and humoral factors. To further explore whether extracellular signal–regulated kinase (ERK) and phosphatidylinositol (PI) 3 kinase specifically regulate different sets of genes, the effects of IGF-1 were inhibited with PD98059 or LY294002. The results showed that the majority of genes regulated by IGF-1 required activation of both ERK and PI 3 kinase. Thus, PI 3 kinase and ERK coordinately mediate the transcriptional regulatory effects of IGF-1 in cardiac muscle cells. These findings provide novel insight into how IGF-1 signaling modulates the programming of cardiac muscle gene expression.

Key Words: insulin-like growth factor • cardiac muscle • gene expression • phosphatidylinositol 3 kinase • mitogen-activated protein kinase

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