title: Hypoxia-induced insulin-like growth factor II contributes to retinal vascularization in ocular development.
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.
authors: Fight against Angiogenesis-Related Blindness Laboratory, Clinical Research Institute, Seoul National University Hospital, Republic of Korea. steph25@snu.ac.kr
authors: Jin Hyoung
authors: JH
authors: Kim
authors: Sung Wook
authors: SW
authors: Park
authors: Young Suk
authors: YS
authors: Yu
authors: Kyu-Won
authors: KW
authors: Kim
authors: Jeong Hun
authors: JH
authors: Kim
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology; D012160:Retina / Q000378:metabolism* / Q000503:physiopathology; D012171:Retinal Vessels / Q000166:cytology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D007335:Insulin-Like Growth Factor II