Upregulation of insulin-like growth factor-1 gene expression in cardiac myocytes by hypoxia : mechanism for its cardioprotective effect

Abstract

    Insulin-like growth factor (IGF)-1 is known to exert beneficial effects on the heart, but its source and function under hypoxia are unknown. We investigated the effect of hypoxia on IGF-1 expression and its role in the regeneration in the heart. Cardiac myocytes and fibroblasts obtained from neonate mice heart were cultured and exposed 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 3 hours after hypoxia concomitantly with the increase in IGFBP3 and VEGF-A mRNA, and returned to the baseline at 24 hours. In contrast, IGF-1 mRNA in cardiac fibroblasts was unchanged by hypoxia, although VEGF-A mRNA was increased. To investigate the role of IGF-1 in the heart regeneration, we measured the gene expressions of stromal cell-derived factor-1 (SDF-1), its receptor CXCR4, and matrix metalloproteinase (MMP)-14 related to cell homing. In cardiac myocytes, SDF-1 and MMP-14 mRNA were increased at 3 hours after hypoxia and tended to be positively correlated with IGF-1 mRNA. These suggest that hypoxia increases IGF-1 expression in cardiac myocytes, and this endogenous IGF-1 may exert beneficial effects on regeneration in the heart.