Hypoxia-induced insulin-like growth factor II contributes to retinal vascularization in ocular development |
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Authors: | Kim Jin Hyoung Park Sung Wook Yu Young Suk Kim Kyu-Won Kim Jeong Hun |
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Institution: | Fight against Angiogenesis-Related Blindness Laboratory, Clinical Research Institute, Seoul National University Hospital, Republic of Korea. steph25@snu.ac.kr |
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Abstract: | In ocular development, retinal physiological hypoxia in response to the retinal metabolic activity controls retinal vascular development, which is regulated by variable angiogenic factors. Herein, we demonstrated that hypoxia-induced IGF-II could contribute to retinal vascularization in ocular development. In the developing retina, IGF-II expression appears to be predominant on retinal vessels, which was chronologically increased and peaked during active retinal angiogenesis similar to VEGF expression. Under hypoxic condition, IGF-II as well as VEGF was significantly up-regulated in retinal vascular endothelial cells. In addition, IGF-II treatment could also increase VEGF expression in retinal vascular endothelial cells. The VEGF expression induced by IGF-II was mediated by ERK-1/2 activation. Moreover, IGF-II strongly promoted angiogenic processes of migration and tube formation of retinal microvascular endothelial cells. In conclusion, our results provided that hypoxia-induced IGF-II may regulate retinal vascular development not only directly by IGF-II-mediated angiogenic activity, but also indirectly by IGF-II-induced VEGF expression. Therefore, the potential contribution of IGF-II to pathological retinal angiogenesis should be furthermore explored for the development of novel treatments to vaso-proliferative retinopathies. |
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Keywords: | Extracellular signal-regulated kinase Hypoxia Insulin-like growth factor II Retinal vascularization Vascular endothelial growth factor |
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