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S. Park, J. Kim, K.-W. Kim, Y. Yu, J. Kim; Hypoxia-Induecd Insulin-Like Growth Factor-2 Regulates Expression of Vascular Endothelial Growth Factor in Retinal Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):57.
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To investigate the role of insulin-like growth factor (IGF)-2 in vascular endothelial growth factor (VEGF) expression in retinal endothelial cells under hypoxia.
In human retinal microvascular endothelial cells, IGF-2 and VEGF expression were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis under hypoxic condition (< 1%). To investigate IGF-2 induced regulation of VEGF expression in HRMEC, western blot analysis for VEGF, ERK-1/2, p-ERK-1/2, Akt, and p-Akt was performed with treatment of IGF-2 (1 to 1000 ng/ml) In addition, VEGF expression in HRMEC was evaluated under hypoxia with treatment of a blocking antibody to IGF-2 by RT-PCR and Western blot analysis.
Under hypoxic condition, IGF-2 and VEGF were up-regulated in HRMEC. VEGF expression increased in dose-dependent manner with treatment of IGF-2, which was accompanied by the significant increase of ERK as well as Akt phosphorylation. Moreover, hypoxia-induced VEGF expression was effectively inhibited by blocking of IGF-2.
Our results suggest that hypoxia-induced IGF-2 could directly regulate VEGF expression in HRMEC via ERK as well as PI3K/Akt pathway. Therefore, IGF-2 might be involved in regulation of developing retinal vessels which is mediated by hypoxia-induced VEGF expression.
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