维普中文期刊产品整合服务

Defective EMC1 drives abnormal retinal angiogenesis via Wnt/β-catenin signaling and may be associated with the pathogenesis of familial exudative vitreoretinopathy

查看全文 作　　者：Shujin [1,2]Li;Mu [1,2]Yang;Rulian [1,2]Zhao;Li [1]Peng;Wenjing [1]Liu;Xiaoyan [1]Jiang;Yunqi [1]He;Erkuan [3]Dai;Lin [1]Zhang;Yeming [1]Yang;Yi [1]Shi;Peiquan [3]Zhao;Zhenglin [1,2]Yang;Xianjun [1,2,4]Zhu 高影响力作者 机构地区：[1]The Sichuan Provincial Key Laboratory for Human Disease Gene Study,Center for Medical Genetics,Department of Laboratory Medicine,Sichuan Provincial People's Hospital,University of Electronic Science and Technology of China,Chengdu,Sichuan 610072,China;[2]Research Unit for Blindness Prevention of the Chinese Academy of Medical Sciences(2019RU026),Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital,Chengdu,Sichuan 610072,China;[3]Department of Ophthalmology,Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China;[4]Key Laboratory of Tibetan Medicine Research,Chinese Academy of Sciences and Qinghai Provincial Key Laboratory of Tibetan Medicine Research,Northwest Institute of Plateau Biology,Xining,Qinghai 810008,China高影响力机构 出　　处：《Genes & Diseases》索引2023年第10卷第6期,共14页高影响力期刊 基　　金：supported by the National Natural Science Foundation of China(No.82101153,82000913,81970841,82121003,and 82071009);the Sichuan Science and Technology Program,China(No.2022YFS0598,2021YFS0386,2021YFS0369,and 2021JDGD0036);the CAMS Innovation Fund for Medical Sciences,China(No.2019-12M-5-032);the Department of Science and Technology of Qinghai Province,China(No.2022-HZ-814);the fund for Sichuan Provincial People's Hospital,China(No.2021QN01);the Department of Chengdu Science and Technology,China(No.2021-YF05-01316-SN);the Huanhua Outstanding Scholar Program for Sichuan Provincial People's Hospital(China)to Xianjun Zhu.The funders had no role in the study design,data collection,analysis,or preparation of the manuscript. 摘　　要：Endoplasmic reticulum(ER)membrane protein complex(EMC)is required for the co-translational insertion of newly synthesized multi-transmembrane proteins.Compromised EMC function in different cell types has been implicated in multiple diseases.Using inducible genetic mouse models,we revealed defects in retinal vascularization upon endothelial cell(EC)specific deletion of Emc1,the largest subunit of EMC.Loss of Emc1 in ECs led to reduced vascular progression and vascular density,diminished tip cell sprouts,and vascular leakage.We then performed an unbiased transcriptomic analysis on human retinal microvascular endothelial cells(HRECs)and revealed a pivotal role of EMC1 in theβ-catenin signaling pathway.Further in-vitro and in-vivo experiments proved that loss of EMC1 led to compromisedβ-catenin signaling activity through reduced expression of Wnt receptor FZD4,which could be restored by lithium chloride(LiCl)treatment.Driven by these findings,we screened genomic DNA samples from familial exudative vitreoretinopathy(FEVR)patients and identified one heterozygous variant in EMC1 that co-segregated with FEVR phenotype in the family.In-vitro expression experiments revealed that this variant allele failed to facilitate the expression of FZD4 on the plasma membrane and activate theβ-catenin signaling pathway,which might be a main cause of FEVR.In conclusion,our findings reveal that variants in EMC1 gene cause compromisedβ-catenin signaling activity,which may be associated with the pathogenesis of FEVR. 关 键 词：ANGIOGENESIS β-catenin signaling EMC1 Familial exudative vitreoretinopathy LICL
相关文献

参考文献(53)

引证文献(1)

网站首页 | 关于我们 | 联系我们 | 产品服务 | 客服中心 | 广告服务 | 版权声明 | 网站联盟 | 友情链接 | 售卡网点

版权所有© 渝B2-20050021-1　渝公网安备 50019002500403号　违法和不良信息举报中心

互联网出版许可证 新出网证(渝)字10号 全国400电话 - 免长途话费