Upregulation of Insulin-Like Growth Factor-1 Gene Expression in Cardiac Myocytes by Hypoxia : Mechanism for Its Cardioprotective Effect

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Insulin-like growth factor （IGF）-1 is known to exert benefi cial eff ects on the heart, but its source andfunction under hypoxia are unknown. We investigated the eff ect of hypoxia on IGF-1 expression and its role in theregeneration in the heart. Cardiac myocytes and fi broblasts obtained from neonate mice heart were cultured andexposed to hypoxia. mRNA of IGF-1, IGF-binding protein 3 （IGFBP3）, and vascular endothelial growth factor-A（VEGF-A） was measured by real-time PCR. In cardiac myocytes, IGF-1 mRNA was increased by 3.5±1.1 fold at 3hours after hypoxia concomitantly with the increase in IGFBP3 and VEGF-A mRNA, and returned to the baseline at24 hours. In contrast, IGF-1 mRNA in cardiac fi broblasts was unchanged by hypoxia, although VEGF-A mRNA wasincreased. To investigate the role of IGF-1 in the heart regeneration, we measured the gene expressions of stromalcell-derived factor-1（ SDF-1）, its receptor CXCR4, and matrix metalloproteinase（ MMP）-14 related to cell homing. Incardiac myocytes, SDF-1 and MMP-14 mRNA were increased at 3 hours after hypoxia and tended to be positivelycorrelated with IGF-1 mRNA. These suggest that hypoxia increases IGF-1 expression in cardiac myocytes, and thisendogenous IGF-1 may exert benefi cial eff ects on regeneration in the heart.
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