P107 constrains expression of Hif target genes in the Vhl^(-/-)mouse retina  

作　　者：Ling Huang Yiwen Hong Wenyu Du Wei Qiang Wenyue Chen Lirong Xiao Yujiao Wang Ran Wei Danian Chen 黄铃;洪邑雯;杜文雨;强薇;谌文悦;肖丽容;王钰娇;魏然;陈大年(Department of Ophthalmology,West China Hospital,Sichuan University,Chengdu 610041,China;Research Laboratory of Ophthalmology and Vision Sciences,Eye Research Institute,West China Hospital,Sichuan University,Chengdu 610041,China)

机构地区：[1]Department of Ophthalmology,West China Hospital,Sichuan University,Chengdu 610041,China [2]Research Laboratory of Ophthalmology and Vision Sciences,Eye Research Institute,West China Hospital,Sichuan University,Chengdu 610041,China

出　　处：《Eye Science》2024年第4期306-318,共13页眼科学报(英文版)

基　　金：supported by National Natural Science Foundation of China(82171063).

摘　　要：Background:Type 3 macular neovascularization(MNV3)is an important subtype of neovascular age-related macular degeneration.Previously,we established an advanced MNV3-like mouse model by knocking out the Vhl,Rb1,and p107 genes in the retinal progenitors(Rb1/p107/Vhl TKO model).This study investigates the role of the p107 protein(also called Rb transcriptional corepressor like 1,Rbl1)on retinal blood vessels in the VhlKO retina.Methods:By breeding the retinal-specific alpha-Cre mice with Vhl^(floxed) mice and p107^(-/-)mice,we got VhlKO,p107KO,and p107/VhlDKO mice.Whole mount retinal IB4 staining,and fundus fluorescein angiography(FFA)were performed to evaluate the retinal vascular vessels.Immunofluorescence staining studied retinal cell types,cell proliferation,and cell death.RNA sequencing,chromatin immunoprecipitation(CHIP),and dual luciferase reporter assay were also performed to study the retinal transcriptome,the binding of p107 protein to the promoter region of Hif target genes,and the effect of the p107 protein on the transcriptional activity of the Hif target genes.Results:p107/VhlDKO mice have delayed regression of hyaloid vessels,retinal degeneration,and retinal neovascularization.The p107 protein significantly inhibits the Hif pathway activity in VhlKO retinas.It can also bind to the promoter regions and suppress the transcriptional activity of several Hif target genes,including Vegfa,Kdr,and Tek.Conclusions:The p107 protein inhibits angiogenesis in the VhlKO retina,as it can bind and inhibit Hif target genes related to retinal angiogenesis.

关 键 词：Type 3 macular neovascularization gene knockout p107 gene Vhl gene Hif gene MNV3 

分 类 号：R73[医药卫生—肿瘤]