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- W2314714693 abstract "<h3>Objectives</h3> Hypoxia inducible factor-1α (HIF-1α) is the key transcription regulator for multiple angiogenic factors, including vascular endothelial growth factor (VEGF). Cellular repressor of E1A-stimulated genes (CREG) has also been identified a potent promoter of angiogenesis. However, the mechanisms by which CREG promotes angiogenesis are not fully understood. Here, we show that CREG is an effective stimulator of HIF-1α under hypoxia in bone marrow-derived mesenchymal stem cells (BMSCs). <h3>Methods</h3> All experiments were performed on rat BMSCs. The level of VEGF was measured by ELISA. The HIF-1α mRNA was analysed by RT-PCR. The level of HIF-1α protein and the mechanisms mediating these proangiogenic effects were determined by Western blotting. <h3>Results</h3> We found that VEGF release from BMSCs was significantly increased in parallel with high level of HIF-1α in BMSCs following anoxia or hypoxia in time-dependent manner. Furthermore, the level of VEGF released from BMSCs overexpressing CREG and the expression of HIF-1α in BMSCs overexpressing CREG were higher than the normal BMSCs under hypoxia. Rather, HIF-1α steady-state mRNA was also affected by CREG. This effect was associated with constitutive activation of phosphatidylinositol 3-kinase (PI3K)/Akt and its effector p70 S6 kinase (p70<sup>S6K</sup>), but not extracellular-signal regulated kinase 1/2. The use of small molecule inhibitors LY294002 or rapamycin to inhibit PI3K/Akt and p70<sup>S6K</sup> activities, respectively, resulted in diminished HIF-1α activation and subsequent VEGF expression. RNA interference-mediated knockdown of HIF-1α suppressed CREG-induced VEGF synthesis and angiogenic tube formation, confirming that the effect was HIF-1α specific. <h3>Conclusions</h3> Overexpressing CREG promote hypoxia-induced VEGF paracrine via HIF-1α in mesenchymal stem cells. therefore, CREG could play a major role in angiogenesis and vascular remodelling." @default.
- W2314714693 created "2016-06-24" @default.
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- W2314714693 date "2013-08-01" @default.
- W2314714693 modified "2023-09-26" @default.
- W2314714693 title "GW24-e1260 Overexpressing cellular repressor of E1A-stimulated genes promote hypoxia-induced VEGF paracrine via HIF-1 in mesenchymal stem cells" @default.
- W2314714693 doi "https://doi.org/10.1136/heartjnl-2013-304613.59" @default.
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