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DOI | 10.1073/pnas.2023290118 |
A specific RIP3+subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism | |
He C.; Liu Y.; Huang Z.; Yang Z.; Zhou T.; Liu S.; Hao Z.; Wang J.; Feng Q.; Liu Y.; Cao Y.; Liu X. | |
发表日期 | 2021 |
ISSN | 00278424 |
卷号 | 118期号:11 |
英文摘要 | Retinal neovascularization is a leading cause of severe visual loss in humans, and molecular mechanisms of microglial activationdriven angiogenesis remain unknown. Using single-cell RNA sequencing, we identified a subpopulation of microglia named sMG2, which highly expressed necroptosis-related genes Rip3 and Mlkl. Genetic and pharmacological loss of function demonstrated that hypoxia-induced microglial activation committed to necroptosis through the RIP1/RIP3-mediated pathway. Specific deletion of Rip3 gene in microglia markedly decreased retinal neovascularization. Furthermore, hypoxia induced explosive release of abundant FGF2 in microglia through RIP3-mediated necroptosis. Importantly, blocking signaling components of the microglia necropotosis-FGF2 axis largely ablated retinal angiogenesis and combination therapy with simultaneously blocking VEGF produced synergistic antiangiogenic effects. Together, our data demonstrate that targeting the microglia necroptosis axis is an antiangiogenesis therapy for retinal neovascular diseases. © 2021 National Academy of Sciences. All rights reserved. |
英文关键词 | FGF2; Microglia; Necroptosis; Retinal angiogenesis; RIP |
语种 | 英语 |
来源期刊 | Proceedings of the National Academy of Sciences of the United States of America |
文献类型 | 期刊论文 |
条目标识符 | http://gcip.llas.ac.cn/handle/2XKMVOVA/180227 |
作者单位 | State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, 17177, Sweden |
推荐引用方式 GB/T 7714 | He C.,Liu Y.,Huang Z.,et al. A specific RIP3+subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism[J],2021,118(11). |
APA | He C..,Liu Y..,Huang Z..,Yang Z..,Zhou T..,...&Liu X..(2021).A specific RIP3+subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism.Proceedings of the National Academy of Sciences of the United States of America,118(11). |
MLA | He C.,et al."A specific RIP3+subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism".Proceedings of the National Academy of Sciences of the United States of America 118.11(2021). |
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