气候变化领域集成服务门户(CCPortal): A specific RIP3+subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism

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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).