1. Interferon-γ inhibits retinal neovascularization in a mouse model of ischemic retinopathy.
- Author
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Jung I, Jung D, Zha Z, Jeong J, Noh S, Shin J, Park JK, Kim KS, Jeong Y, Hur J, Baek MC, Diaz-Aguilar S, Aguilar E, Friedlander M, Bucher F, and Yea K
- Subjects
- Animals, Cell Movement drug effects, Cell Proliferation drug effects, Disease Models, Animal, Down-Regulation drug effects, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells metabolism, Humans, Hypoxia complications, Interferon-gamma administration & dosage, Interferon-gamma pharmacology, Intravitreal Injections, Mice, Neovascularization, Physiologic drug effects, Retina drug effects, Retina pathology, Retina physiopathology, Retinal Neovascularization physiopathology, STAT1 Transcription Factor metabolism, Signal Transduction drug effects, Interferon-gamma therapeutic use, Ischemia complications, Retinal Neovascularization complications, Retinal Neovascularization drug therapy
- Abstract
Interferon-γ (IFNG) is one of the key cytokines that regulates both innate and adaptive immune responses in the body. However, the role of IFNG in the regulation of vascularization, especially in the context of Vascular endothelial growth factor A (VEGFa)-induced angiogenesis is not clarified. Here, we report that IFNG shows potent anti-angiogenic potential against VEGFa-induced angiogenesis. IFNG significantly inhibited proliferation, migration, and tube formation of Human umbilical vein endothelial cells (HUVECs) both under basal and VEGFa-treated conditions. Intriguingly, Knockdown (KD) of STAT1 abolished the inhibitory effect of IFNG on VEGFa-induced angiogenic processes in HUVECs. Furthermore, IFNG exhibited potent anti-angiogenic efficacy in the mouse model of oxygen-induced retinopathy (OIR), an in vivo model for hypoxia-induced retinal neovascularization, without induction of functional side effects. Taken together, these results show that IFNG plays a crucial role in the regulation of VEGFa-dependent angiogenesis, suggesting its potential therapeutic applicability in neovascular diseases., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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